{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:48:13Z","timestamp":1790830093440,"version":"4.1.0"},"reference-count":225,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM144399"],"award-info":[{"award-number":["R01 GM144399"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["132235-RSG-18-037-DMC"],"award-info":[{"award-number":["132235-RSG-18-037-DMC"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["R01 GM144399"],"award-info":[{"award-number":["R01 GM144399"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["132235-RSG-18-037-DMC"],"award-info":[{"award-number":["132235-RSG-18-037-DMC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Renaissance School of Medicine at Stony Brook University","award":["R01 GM144399"],"award-info":[{"award-number":["R01 GM144399"]}]},{"name":"Renaissance School of Medicine at Stony Brook University","award":["132235-RSG-18-037-DMC"],"award-info":[{"award-number":["132235-RSG-18-037-DMC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DNA replication is a tightly controlled process that ensures the faithful duplication of the genome. However, DNA damage arising from both endogenous and exogenous assaults gives rise to DNA replication stress associated with replication fork slowing or stalling. Therefore, protecting the stressed fork while prompting its recovery to complete DNA replication is critical for safeguarding genomic integrity and cell survival. Specifically, the plasticity of the replication fork in engaging distinct DNA damage tolerance mechanisms, including fork reversal, repriming, and translesion DNA synthesis, enables cells to overcome a variety of replication obstacles. Furthermore, stretches of single-stranded DNA generated upon fork stalling trigger the activation of the ATR kinase, which coordinates the cellular responses to replication stress by stabilizing the replication fork, promoting DNA repair, and controlling cell cycle and replication origin firing. Deregulation of the ATR checkpoint and aberrant levels of chronic replication stress is a common characteristic of cancer and a point of vulnerability being exploited in cancer therapy. Here, we discuss the various adaptive responses of a replication fork to replication stress and the roles of ATR signaling that bring fork stabilization mechanisms together. We also review how this knowledge is being harnessed for the development of checkpoint inhibitors to trigger the replication catastrophe of cancer cells.<\/jats:p>","DOI":"10.3390\/ijms241310488","type":"journal-article","created":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T01:54:56Z","timestamp":1687485296000},"page":"10488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1419-0859","authenticated-orcid":false,"given":"Joanne","family":"Saldanha","sequence":"first","affiliation":[{"name":"The Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA"},{"name":"Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-7043","authenticated-orcid":false,"given":"Julie","family":"Rageul","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinal A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-6373","authenticated-orcid":false,"given":"Hyungjin","family":"Kim","sequence":"additional","affiliation":[{"name":"The Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA"},{"name":"Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA"},{"name":"Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/bies.10208","article-title":"Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem","volume":"25","author":"Hyrien","year":"2003","journal-title":"Bioessays"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nrm4002","article-title":"DNA replication origin activation in space and time","volume":"16","author":"Fragkos","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1101\/gad.457807","article-title":"Dormant origins licensed by excess Mcm2\u20137 are required for human cells to survive replicative stress","volume":"21","author":"Ge","year":"2007","journal-title":"Genes Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev-biochem-061516-044709","article-title":"Eukaryotic DNA Replication Fork","volume":"86","author":"Burgers","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1101\/gad.298232.117","article-title":"From structure to mechanism-understanding initiation of DNA replication","volume":"31","author":"Riera","year":"2017","journal-title":"Genes Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-biochem-072321-110228","article-title":"The Initiation of Eukaryotic DNA Replication","volume":"91","author":"Costa","year":"2022","journal-title":"Annu. Rev. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-022-04698-x","article-title":"CDC7-independent G1\/S transition revealed by targeted protein degradation","volume":"605","author":"Suski","year":"2022","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e58622","DOI":"10.7554\/eLife.58622","article-title":"The dynamic nature of the human origin recognition complex revealed through five cryoEM structures","volume":"9","author":"Jaremko","year":"2020","journal-title":"eLife"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S1097-2765(02)00467-7","article-title":"Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication","volume":"9","author":"Mendez","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1038\/s41467-021-24199-1","article-title":"The structure of ORC-Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6","volume":"12","author":"Feng","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.molcel.2005.11.023","article-title":"Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase","volume":"21","author":"Randell","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0960-9822(00)00337-7","article-title":"Clb\/Cdc28 kinases promote nuclear export of the replication initiator proteins Mcm2\u20137","volume":"10","author":"Nguyen","year":"2000","journal-title":"Curr. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1093\/emboj\/18.2.396","article-title":"Phosphorylation of mammalian CDC6 by Cyclin A\/CDK2 regulates its subcellular localization","volume":"18","author":"Petersen","year":"1999","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1242\/jcs.02851","article-title":"Ubiquitylation, phosphorylation and Orc2 modulate the subcellular location of Orc1 and prevent it from inducing apoptosis","volume":"119","author":"Saha","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1101\/gad.2068611","article-title":"Mechanism of CRL4(Cdt2), a PCNA-dependent E3 ubiquitin ligase","volume":"25","author":"Havens","year":"2011","journal-title":"Genes Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1126\/science.290.5500.2309","article-title":"Inhibition of Eukaryotic DNA Replication by Geminin Binding to Cdt1","volume":"290","author":"Wohlschlegel","year":"2000","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cell.2011.06.012","article-title":"Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases","volume":"146","author":"Heller","year":"2011","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.molcel.2009.12.030","article-title":"Activation of the MCM2-7 Helicase by Association with Cdc45 and GINS Proteins","volume":"37","author":"Ilves","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.molcel.2006.07.033","article-title":"Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression","volume":"24","author":"Sheu","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.cell.2009.12.049","article-title":"Treslin collaborates with TopBP1 in triggering the initiation of DNA replication","volume":"140","author":"Kumagai","year":"2010","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1101\/gad.1883410","article-title":"CDK-dependent complex formation between replication proteins Dpb11, Sld2, Pol (epsilon, and GINS in budding yeast","volume":"24","author":"Muramatsu","year":"2010","journal-title":"Genes Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.cell.2005.05.015","article-title":"Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome","volume":"121","author":"Sangrithi","year":"2005","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nature05465","article-title":"CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast","volume":"445","author":"Tanaka","year":"2007","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nature05432","article-title":"Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast","volume":"445","author":"Zegerman","year":"2007","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.15252\/embr.201744206","article-title":"Pre-initiation complex assembly functions as a molecular switch that splits the Mcm2-7 double hexamer","volume":"18","author":"Araki","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nature25787","article-title":"The mechanism of eukaryotic CMG helicase activation","volume":"555","author":"Douglas","year":"2018","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.cell.2011.07.045","article-title":"Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase","volume":"146","author":"Fu","year":"2011","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s00018-023-04738-3","article-title":"The TIMELESS effort for timely DNA replication and protection","volume":"80","author":"Patel","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.4161\/cc.21989","article-title":"Local and global functions of Timeless and Tipin in replication fork protection","volume":"11","author":"Leman","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.molcel.2015.07.031","article-title":"Timeless Interacts with PARP-1 to Promote Homologous Recombination Repair","volume":"60","author":"Xie","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1093\/nar\/gkv1112","article-title":"Tim\/Timeless, a member of the replication fork protection complex, operates with the Warsaw breakage syndrome DNA helicase DDX11 in the same fork recovery pathway","volume":"44","author":"Cali","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.1038\/s41467-020-19162-5","article-title":"SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks","volume":"11","author":"Rageul","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"102268","DOI":"10.1016\/j.jbc.2022.102268","article-title":"Extended DNA-binding interfaces beyond the canonical SAP domain contribute to the function of replication stress regulator SDE2 at DNA replication forks","volume":"298","author":"Weinheimer","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1091\/mbc.e07-10-1035","article-title":"Claspin promotes normal replication fork rates in human cells","volume":"19","author":"Petermann","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.molcel.2005.07.028","article-title":"Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53","volume":"19","author":"Tourriere","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1126\/science.aao3172","article-title":"Redox-sensitive alteration of replisome architecture safeguards genome integrity","volume":"358","author":"Somyajit","year":"2017","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1128\/MCB.02190-06","article-title":"The human Tim\/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement","volume":"27","author":"Chastain","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.molcel.2020.04.012","article-title":"Cryo-EM Structure of the Fork Protection Complex Bound to CMG at a Replication Fork","volume":"78","author":"Baretic","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e108819","DOI":"10.15252\/embj.2021108819","article-title":"Structure of a human replisome shows the organisation and interactions of a DNA replication machine","volume":"40","author":"Jones","year":"2021","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1073\/pnas.1222494110","article-title":"Human Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases","volume":"110","author":"Cho","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature14285","article-title":"Regulated eukaryotic DNA replication origin firing with purified proteins","volume":"519","author":"Yeeles","year":"2015","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.molcel.2016.11.017","article-title":"How the Eukaryotic Replisome Achieves Rapid and Efficient DNA Replication","volume":"65","author":"Yeeles","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/nature01900","article-title":"S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex","volume":"424","author":"Katou","year":"2003","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Gadaleta, M.C., Das, M.M., Tanizawa, H., Chang, Y.T., Noma, K., Nakamura, T.M., and Noguchi, E. (2016). Swi1Timeless Prevents Repeat Instability at Fission Yeast Telomeres. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005943"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nsmb.1527","article-title":"Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility","volume":"16","author":"Voineagu","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e104185","DOI":"10.15252\/embj.2019104185","article-title":"Timeless couples G-quadruplex detection with processing by DDX11 helicase during DNA replication","volume":"39","author":"Lerner","year":"2020","journal-title":"EMBO J."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Cortone, G., Zheng, G., Pensieri, P., Chiappetta, V., Tate, R., Malacaria, E., Pichierri, P., Yu, H., and Pisani, F.M. (2018). Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007622"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0092-8674(00)00063-5","article-title":"swi1 and swi3 perform imprinting, pausing, and termination of DNA replication in S. pombe","volume":"102","author":"Dalgaard","year":"2000","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"14085","DOI":"10.1073\/pnas.0406037101","article-title":"swi1- and swi3-dependent and independent replication fork arrest at the ribosomal DNA of Schizosaccharomyces pombe","volume":"101","author":"Krings","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"E4565","DOI":"10.1073\/pnas.1505356112","article-title":"Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability","volume":"112","author":"Schalbetter","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/(SICI)1097-0061(19990115)15:1<35::AID-YEA340>3.0.CO;2-R","article-title":"Identification and characterization of the genes for two topoisomerase I-interacting proteins from Saccharomyces cerevisiae","volume":"15","author":"Park","year":"1999","journal-title":"Yeast"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nrm3935","article-title":"Replication fork reversal in eukaryotes: From dead end to dynamic response","volume":"16","author":"Neelsen","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1126\/science.add7328","article-title":"RAD51 bypasses the CMG helicase to promote replication fork reversal","volume":"380","author":"Liu","year":"2023","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/nsmb.1904","article-title":"Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA","volume":"17","author":"Liu","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.molcel.2012.05.025","article-title":"The HARP-like domain-containing protein AH2\/ZRANB3 binds to PCNA and participates in cellular response to replication stress","volume":"47","author":"Yuan","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1074\/jbc.M114.627083","article-title":"High-affinity DNA-binding domains of replication protein A (RPA) direct SMARCAL1-dependent replication fork remodeling","volume":"290","author":"Bhat","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1101\/gad.1832309","article-title":"The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart","volume":"23","author":"Ciccia","year":"2009","journal-title":"Genes Dev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.celrep.2013.05.002","article-title":"Substrate-selective repair and restart of replication forks by DNA translocases","volume":"3","author":"Couch","year":"2013","journal-title":"Cell Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.molcel.2017.08.010","article-title":"Replication fork slowing and reversal upon DNA damage require PCNA polyubiquitination and ZRANB3 DNA translocase activity","volume":"67","author":"Vujanovic","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.molcel.2011.02.026","article-title":"SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis","volume":"42","author":"Lin","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_61","first-page":"11340","article-title":"Regulation of HLTF-mediated PCNA polyubiquitination by RFC and PCNA monoubiquitination levels determines choice of damage tolerance pathway","volume":"46","author":"Masuda","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.molcel.2015.05.013","article-title":"HLTF\u2019s Ancient HIRAN Domain Binds 3 \u2018 DNA Ends to Drive Replication Fork Reversal","volume":"58","author":"Kile","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1038\/emboj.2009.206","article-title":"PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination","volume":"28","author":"Bryant","year":"2009","journal-title":"EMBO J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/s41467-017-01180-5","article-title":"MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells","volume":"8","author":"Lemacon","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/nature18325","article-title":"Replication fork stability confers chemoresistance in BRCA-deficient cells","volume":"535","author":"Chaudhuri","year":"2016","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ccr.2012.05.015","article-title":"A Distinct Replication Fork Protection Pathway Connects Fanconi Anemia Tumor Suppressors to RAD51-BRCA1\/2","volume":"22","author":"Schlacher","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.molcel.2015.06.007","article-title":"BOD1L Is Required to Suppress Deleterious Resection of Stressed Replication Forks","volume":"59","author":"Higgs","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.molcel.2018.05.018","article-title":"Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome Chaperone Activity of FANCD2","volume":"71","author":"Higgs","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1101\/gad.299172.117","article-title":"Abro1 maintains genome stability and limits replication stress by protecting replication fork stability","volume":"31","author":"Xu","year":"2017","journal-title":"Genes Dev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nsmb.2501","article-title":"Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition","volume":"20","author":"Berti","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1083\/jcb.201406100","article-title":"DNA2 drives processing and restart of reversed replication forks in human cells","volume":"208","author":"Thangavel","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.molcel.2016.10.038","article-title":"Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks","volume":"64","author":"Sotiriou","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.molcel.2013.09.025","article-title":"PrimPol, an Archaic Primase\/Polymerase Operating in Human Cells","volume":"52","author":"Reyes","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.molcel.2013.10.035","article-title":"PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication","volume":"52","author":"Bianchi","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nsmb.2719","article-title":"Repriming of DNA synthesis at stalled replication forks by human PrimPol","volume":"20","author":"Blanco","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1038\/s41467-021-24317-z","article-title":"Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase","volume":"12","author":"Rechkoblit","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/s41598-018-37439-0","article-title":"A cancer-associated point mutation disables the steric gate of human PrimPol","volume":"9","author":"Calvo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1080\/15384101.2016.1191711","article-title":"Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides","volume":"15","author":"Kobayashi","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"eabh1004","DOI":"10.1126\/sciadv.abh1004","article-title":"PLK1 regulates the PrimPol damage tolerance pathway during the cell cycle","volume":"7","author":"Bailey","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1093\/nar\/gkw175","article-title":"PolDIP2 interacts with human PrimPol and enhances its DNA polymerase activities","volume":"44","author":"Guilliam","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"12711","DOI":"10.1093\/nar\/gkaa1090","article-title":"The deubiquitinase USP36 Regulates DNA replication stress and confers therapeutic resistance through PrimPol stabilization","volume":"48","author":"Yan","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5966","DOI":"10.1038\/s41467-021-26227-6","article-title":"BRCA2 associates with MCM10 to suppress PRIMPOL-mediated repriming and single-stranded gap formation after DNA damage","volume":"12","author":"Kang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"eade7997","DOI":"10.1126\/sciadv.ade7997","article-title":"Polymerase iota (Pol iota) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability","volume":"9","author":"Mansilla","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Lim, P.X., Zaman, M., and Jasin, M. (2023). BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair. bioRxiv.","DOI":"10.1101\/2023.04.11.536470"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"110879","DOI":"10.1016\/j.celrep.2022.110879","article-title":"MDM2 binds and ubiquitinates PARP1 to enhance DNA replication fork progression","volume":"39","author":"Giansanti","year":"2022","journal-title":"Cell Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0959-440X(02)00003-9","article-title":"Damage repair DNA polymerases Y","volume":"13","author":"Yang","year":"2003","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/nchembio.139","article-title":"DNA damage tolerance: When it\u2019s OK to make mistakes","volume":"5","author":"Chang","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/s41594-020-0418-4","article-title":"Reconstitution of translesion synthesis reveals a mechanism of eukaryotic DNA replication restart","volume":"27","author":"Guilliam","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1016\/j.molcel.2021.09.013","article-title":"Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells","volume":"81","author":"Tirman","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/ncb1378","article-title":"Regulation of monoubiquitinated PCNA by DUB autocleavage","volume":"8","author":"Huang","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/emboj.2011.457","article-title":"Dysregulation of DNA polymerase kappa recruitment to replication forks results in genomic instability","volume":"31","author":"Jones","year":"2012","journal-title":"EMBO J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1038\/s41467-022-29369-3","article-title":"USP1-trapping lesions as a source of DNA replication stress and genomic instability","volume":"13","author":"Coleman","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.molcel.2018.10.045","article-title":"USP1 Is Required for Replication Fork Protection in BRCA1-Deficient Tumors","volume":"72","author":"Lim","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1128\/MCB.00071-09","article-title":"Separate domains of Rev1 mediate two modes of DNA damage bypass in mammalian cells","volume":"29","author":"Jansen","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5717","DOI":"10.1093\/nar\/gkw280","article-title":"Translesion synthesis mechanisms depend on the nature of DNA damage in UV-irradiated human cells","volume":"44","author":"Quinet","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.molcel.2019.10.008","article-title":"PRIMPOL-mediated adaptive response suppresses replication fork reversal in BRCA-deficient cells","volume":"77","author":"Quinet","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e106355","DOI":"10.15252\/embj.2020106355","article-title":"PrimPol-mediated repriming facilitates replication traverse of DNA interstrand crosslinks","volume":"40","author":"Mutreja","year":"2021","journal-title":"EMBO J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1158\/0008-5472.CAN-20-1602","article-title":"Replication Gaps Underlie BRCA Deficiency and Therapy ResponseGaps Underlie BRCA Deficiency and Therapy Response","volume":"81","author":"Panzarino","year":"2021","journal-title":"Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.molcel.2020.04.031","article-title":"HLTF Promotes Fork Reversal, Limiting Replication Stress Resistance and Preventing Multiple Mechanisms of Unrestrained DNA Synthesis","volume":"78","author":"Bai","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.molcel.2020.12.010","article-title":"CARM1 regulates replication fork speed and stress response by stimulating PARP1","volume":"81","author":"Genois","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"E6624","DOI":"10.1073\/pnas.1508543112","article-title":"Rad51 recombinase prevents Mre11 nuclease-dependent degradation and excessive PrimPol-mediated elongation of nascent DNA after UV irradiation","volume":"112","author":"Vallerga","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1038\/onc.2010.18","article-title":"Targeting the FANCJ\u2013BRCA1 interaction promotes a switch from recombination to pol\u03b7-dependent bypass","volume":"29","author":"Xie","year":"2010","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"eaaz7808","DOI":"10.1126\/sciadv.aaz7808","article-title":"Inhibition of the translesion synthesis polymerase REV1 exploits replication gaps as a cancer vulnerability","volume":"6","author":"Nayak","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1080\/10409238.2017.1380597","article-title":"Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability","volume":"52","author":"Poole","year":"2017","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1093\/nar\/gkz056","article-title":"PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells","volume":"47","author":"Bailey","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1126\/science.1083430","article-title":"Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes","volume":"300","author":"Zou","year":"2003","journal-title":"Science"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/nrm.2017.67","article-title":"The essential kinase ATR: Ensuring faithful duplication of a challenging genome","volume":"18","author":"Saldivar","year":"2017","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"R33","DOI":"10.1016\/j.cub.2016.11.025","article-title":"DNA Replication Checkpoint: New ATR Activator Identified","volume":"27","author":"Zou","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8395","DOI":"10.1074\/jbc.RA119.008154","article-title":"Common motifs in ETAA1 and TOPBP1 required for ATR kinase activation","volume":"294","author":"Thada","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1101\/gad.1547007","article-title":"The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1","volume":"21","author":"Delacroix","year":"2007","journal-title":"Genes Dev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.cell.2005.12.041","article-title":"TopBP1 activates the ATR-ATRIP complex","volume":"124","author":"Kumagai","year":"2006","journal-title":"Cell"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.molcel.2013.09.021","article-title":"The DNA translocase FANCM\/MHF promotes replication traverse of DNA interstrand crosslinks","volume":"52","author":"Huang","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.molcel.2010.07.005","article-title":"The FANCM\/FAAP24 complex is required for the DNA interstrand crosslink-induced checkpoint response","volume":"39","author":"Huang","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/ncb3415","article-title":"ETAA1 acts at stalled replication forks to maintain genome integrity","volume":"18","author":"Bass","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1038\/ncb3422","article-title":"Activation of the ATR kinase by the RPA-binding protein ETAA1","volume":"18","author":"Haahr","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1126\/science.aap9346","article-title":"An intrinsic S\/G(2) checkpoint enforced by ATR","volume":"361","author":"Saldivar","year":"2018","journal-title":"Science"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1083\/jcb.201810058","article-title":"Quantitative phosphoproteomics reveals mitotic function of the ATR activator ETAA1","volume":"218","author":"Bass","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.molcel.2015.07.029","article-title":"Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase","volume":"59","author":"Buisson","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.1038\/s41467-018-07798-3","article-title":"Kinase-dead ATR differs from ATR loss by limiting the dynamic exchange of ATR and RPA","volume":"9","author":"Menolfi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1038\/onc.2009.102","article-title":"Chk1 C-terminal regulatory phosphorylation mediates checkpoint activation by de-repression of Chk1 catalytic activity","volume":"28","author":"Walker","year":"2009","journal-title":"Oncogene"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"20752","DOI":"10.1073\/pnas.0806917106","article-title":"Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control","volume":"105","author":"Wilsker","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"19024","DOI":"10.1074\/jbc.M117.811265","article-title":"Intramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase-associated 1 domain","volume":"292","author":"Emptage","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"16562","DOI":"10.1074\/jbc.M110.110304","article-title":"Tipin-replication protein A interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stress","volume":"285","author":"Kemp","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"30057","DOI":"10.1074\/jbc.M301136200","article-title":"Human claspin is required for replication checkpoint control","volume":"278","author":"Chini","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S1097-2765(05)00092-4","article-title":"Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts","volume":"6","author":"Kumagai","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"6484","DOI":"10.1073\/pnas.0401847101","article-title":"Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation","volume":"101","author":"Lin","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"33107","DOI":"10.1074\/jbc.M109.064485","article-title":"Reconstitution of human claspin-mediated phosphorylation of Chk1 by the ATR (ataxia telangiectasia-mutated and rad3-related) checkpoint kinase","volume":"284","author":"Sercin","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6056","DOI":"10.1128\/MCB.00492-06","article-title":"Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation","volume":"26","author":"Liu","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.str.2021.03.007","article-title":"Structural basis for recruitment of the CHK1 DNA damage kinase by the CLASPIN scaffold protein","volume":"29","author":"Day","year":"2021","journal-title":"Structure"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.15252\/embj.201488016","article-title":"And-1 coordinates with Claspin for efficient Chk1 activation in response to replication stress","volume":"34","author":"Hao","year":"2015","journal-title":"EMBO J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1126\/science.288.5470.1425","article-title":"Rapid destruction of human Cdc25A in response to DNA damage","volume":"288","author":"Mailand","year":"2000","journal-title":"Science"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S1535-6108(03)00048-5","article-title":"Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A","volume":"3","author":"Sorensen","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"469","DOI":"10.4161\/cc.3.4.770","article-title":"Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation","volume":"3","author":"Donzelli","year":"2004","journal-title":"Cell Cycle"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature02082","article-title":"Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage","volume":"426","author":"Busino","year":"2003","journal-title":"Nature"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/16488","article-title":"Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein","volume":"397","author":"Furnari","year":"1999","journal-title":"Nature"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1126\/science.277.5331.1501","article-title":"Mitotic and G2 checkpoint control: Regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216","volume":"277","author":"Peng","year":"1997","journal-title":"Science"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/ncb1165","article-title":"Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase","volume":"6","author":"Kramer","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1242\/jcs.03200","article-title":"CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage","volume":"119","author":"Schmitt","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"102655","DOI":"10.1016\/j.dnarep.2019.102655","article-title":"Dormant origin signaling during unperturbed replication","volume":"81","author":"Moiseeva","year":"2019","journal-title":"DNA Repair"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/s41586-020-2842-3","article-title":"Equilibrium between nascent and parental MCM proteins protects replicating genomes","volume":"587","author":"Sedlackova","year":"2020","journal-title":"Nature"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"28071","DOI":"10.1074\/jbc.M401574200","article-title":"Control of replication origin density and firing time in Xenopus egg extracts: Role of a caffeine-sensitive, ATR-dependent checkpoint","volume":"279","author":"Marheineke","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ncb1145","article-title":"ATR and ATM regulate the timing of DNA replication origin firing","volume":"6","author":"Shechter","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1073\/pnas.0809350106","article-title":"Cyclin A-Cdk1 regulates the origin firing program in mammalian cells","volume":"106","author":"Katsuno","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.1128\/MCB.00412-12","article-title":"Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption","volume":"32","author":"Beck","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1073\/pnas.1005031107","article-title":"Chk1 promotes replication fork progression by controlling replication initiation","volume":"107","author":"Petermann","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"13374","DOI":"10.1073\/pnas.1903418116","article-title":"An ATR and CHK1 kinase signaling mechanism that limits origin firing during unperturbed DNA replication","volume":"116","author":"Moiseeva","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nature09377","article-title":"Damage-induced phosphorylation of Sld3 is important to block late origin firing","volume":"467","author":"Maas","year":"2010","journal-title":"Nature"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"961","DOI":"10.15252\/embj.201593552","article-title":"Phosphopeptide binding by Sld3 links Dbf4-dependent kinase to MCM replicative helicase activation","volume":"35","author":"Deegan","year":"2016","journal-title":"EMBO J."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"9458","DOI":"10.1074\/jbc.M611292200","article-title":"Cdc7-Dbf4 and the human S checkpoint response to UVC","volume":"282","author":"Heffernan","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature09373","article-title":"Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation","volume":"467","author":"Zegerman","year":"2010","journal-title":"Nature"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"14795","DOI":"10.1073\/pnas.182557299","article-title":"Disruption of the checkpoint kinase 1\/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints","volume":"99","author":"Zhao","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature09350","article-title":"Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint","volume":"467","author":"Liu","year":"2010","journal-title":"Nature"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.molcel.2014.12.003","article-title":"Interaction of Chk1 with Treslin negatively regulates the initiation of chromosomal DNA replication","volume":"57","author":"Guo","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1083\/jcb.201007074","article-title":"Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories","volume":"191","author":"Ge","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1038\/sj.emboj.7601714","article-title":"Chk1 regulates the density of active replication origins during the vertebrate S phase","volume":"26","author":"Petermann","year":"2007","journal-title":"EMBO J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.4161\/cc.5.19.3256","article-title":"Evidence that the ATR\/Chk1 pathway maintains normal replication fork progression during unperturbed S phase","volume":"5","author":"Petermann","year":"2006","journal-title":"Cell Cycle"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1128\/MCB.26.8.3319-3326.2006","article-title":"Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase","volume":"26","author":"Petermann","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"10078","DOI":"10.1073\/pnas.0403410101","article-title":"Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases","volume":"101","author":"Cortez","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/emboj.2008.29","article-title":"Plx1 is required for chromosomal DNA replication under stressful conditions","volume":"27","author":"Trenz","year":"2008","journal-title":"EMBO J."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.molcel.2015.02.031","article-title":"ATR-mediated phosphorylation of FANCI regulates dormant origin firing in response to replication stress","volume":"58","author":"Chen","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1101\/gad.224568.113","article-title":"ATR-Chk1-APC\/CCdh1-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress","volume":"27","author":"Yamada","year":"2013","journal-title":"Genes Dev."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.molcel.2012.01.007","article-title":"Replisome stability at defective DNA replication forks is independent of S phase checkpoint kinases","volume":"45","author":"Katou","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.molcel.2015.07.030","article-title":"The Replication Checkpoint Prevents Two Types of Fork Collapse without Regulating Replisome Stability","volume":"59","author":"Dungrawala","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/35087613","article-title":"The DNA replication checkpoint response stabilizes stalled replication forks","volume":"412","author":"Lopes","year":"2001","journal-title":"Nature"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/35087607","article-title":"Regulation of DNA replication fork progression through damaged DNA by the Mec1\/Rad53 checkpoint","volume":"412","author":"Tercero","year":"2001","journal-title":"Nature"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0092-8674(02)01113-3","article-title":"ATR regulates fragile site stability","volume":"111","author":"Casper","year":"2002","journal-title":"Cell"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1128\/MCB.25.9.3553-3562.2005","article-title":"Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage","volume":"25","author":"Syljuasen","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1101\/gad.214080.113","article-title":"ATR phosphorylates SMARCAL1 to prevent replication fork collapse","volume":"27","author":"Couch","year":"2013","journal-title":"Genes Dev."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.molcel.2004.11.032","article-title":"Exo1 processes stalled replication forks and counteracts fork reversal in checkpoint-defective cells","volume":"17","author":"Fachinetti","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1126\/science.1074023","article-title":"Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects","volume":"297","author":"Sogo","year":"2002","journal-title":"Science"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1101\/gad.1839909","article-title":"The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks","volume":"23","author":"Bansbach","year":"2009","journal-title":"Genes Dev."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1101\/gad.223180.113","article-title":"RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells","volume":"27","author":"Ragland","year":"2013","journal-title":"Genes Dev."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.molcel.2013.08.035","article-title":"Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells","volume":"52","author":"Wyatt","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1083\/jcb.200905059","article-title":"Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase","volume":"188","author":"Beck","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1083\/jcb.201101047","article-title":"Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease","volume":"194","author":"Martin","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Forment, J.V., Blasius, M., Guerini, I., and Jackson, S.P. (2011). Structure-specific DNA endonuclease Mus81\/Eme1 generates DNA damage caused by Chk1 inactivation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023517"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Murfuni, I., Basile, G., Subramanyam, S., Malacaria, E., Bignami, M., Spies, M., Franchitto, A., and Pichierri, P. (2013). Survival of the replication checkpoint deficient cells requires MUS81-RAD52 function. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003910"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.devcel.2016.11.017","article-title":"A Mechanism for Controlled Breakage of Under-replicated Chromosomes during Mitosis","volume":"39","author":"Duda","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/nsmb1313","article-title":"The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks","volume":"14","author":"Hanada","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.celrep.2015.12.093","article-title":"Signaling from Mus81-Eme2-Dependent DNA Damage Elicited by Chk1 Deficiency Modulates Replication Fork Speed and Origin Usage","volume":"14","author":"Techer","year":"2016","journal-title":"Cell Rep."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Thompson, R., Montano, R., and Eastman, A. (2012). The Mre11 nuclease is critical for the sensitivity of cells to Chk1 inhibition. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044021"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"eabm0314","DOI":"10.1126\/sciadv.abm0314","article-title":"CHK1 phosphorylates PRIMPOL to promote replication stress tolerance","volume":"8","author":"Mehta","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1083\/jcb.201008076","article-title":"ATR-mediated phosphorylation of DNA polymerase eta is needed for efficient recovery from UV damage","volume":"192","author":"Gohler","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.cub.2006.01.063","article-title":"ATR homolog Mec1 controls association of DNA polymerase zeta-Rev1 complex with regions near a double-strand break","volume":"16","author":"Hirano","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1038\/emboj.2010.205","article-title":"ATR and ATM differently regulate WRN to prevent DSBs at stalled replication forks and promote replication fork recovery","volume":"29","author":"Ammazzalorso","year":"2010","journal-title":"EMBO J."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1128\/MCB.24.3.1279-1291.2004","article-title":"Phosphorylation of the Bloom\u2019s syndrome helicase and its role in recovery from S-phase arrest","volume":"24","author":"Davies","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1016\/j.celrep.2018.08.019","article-title":"ATR-Mediated Global Fork Slowing and Reversal Assist Fork Traverse and Prevent Chromosomal Breakage at DNA Interstrand Cross-Links","volume":"24","author":"Mutreja","year":"2018","journal-title":"Cell Rep."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.molcel.2017.09.018","article-title":"Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress","volume":"68","author":"Gan","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"e2109334118","DOI":"10.1073\/pnas.2109334118","article-title":"A mechanism for Rad53 to couple leading- and lagging-strand DNA synthesis under replication stress in budding yeast","volume":"118","author":"Yu","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"e69726","DOI":"10.7554\/eLife.69726","article-title":"Rad53 checkpoint kinase regulation of DNA replication fork rate via Mrc1 phosphorylation","volume":"10","author":"McClure","year":"2021","journal-title":"eLife"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1016\/j.celrep.2020.01.067","article-title":"Physiological Tolerance to ssDNA Enables Strand Uncoupling during DNA Replication","volume":"30","author":"Ercilla","year":"2020","journal-title":"Cell Rep."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.molcel.2013.07.023","article-title":"FANCD2 binds MCM proteins and controls replisome function upon activation of s phase checkpoint signaling","volume":"51","author":"Lossaint","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.cell.2013.10.043","article-title":"ATR prohibits replication catastrophe by preventing global exhaustion of RPA","volume":"155","author":"Toledo","year":"2013","journal-title":"Cell"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1016\/j.molcel.2021.08.009","article-title":"A basal-level activity of ATR links replication fork surveillance and stress response","volume":"81","author":"Yin","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Patel, J.A., Zezelic, C., Rageul, J., Saldanha, J., Khan, A., and Kim, H. (2023). Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe. Nucleic Acids Res., gkad363.","DOI":"10.1093\/nar\/gkad363"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.molcel.2017.05.001","article-title":"Replication Catastrophe: When a Checkpoint Fails because of Exhaustion","volume":"66","author":"Toledo","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/s13046-021-02124-0","article-title":"Replication catastrophe is responsible for intrinsic PAR glycohydrolase inhibitor-sensitivity in patient-derived ovarian cancer models","volume":"40","author":"Morgan","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.ccell.2019.02.004","article-title":"DNA Replication Vulnerabilities Render Ovarian Cancer Cells Sensitive to Poly(ADP-Ribose) Glycohydrolase Inhibitors","volume":"35","author":"Pillay","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1534\/g3.111.000554","article-title":"Replication stress-induced chromosome breakage is correlated with replication fork progression and is preceded by single-stranded DNA formation","volume":"1","author":"Feng","year":"2011","journal-title":"G3"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nrd4553","article-title":"Exploiting replicative stress to treat cancer","volume":"14","author":"Dobbelstein","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1038\/cddis.2012.181","article-title":"Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation","volume":"3","author":"Fokas","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3892\/or.2022.8289","article-title":"ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting repair of DNA damage","volume":"47","author":"Suzuki","year":"2022","journal-title":"Oncol. Rep."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"4869","DOI":"10.1038\/s41388-020-1328-y","article-title":"Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells","volume":"39","author":"Lloyd","year":"2020","journal-title":"Oncogene"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1158\/0008-5472.CAN-21-2997","article-title":"ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib","volume":"82","author":"Wilson","year":"2022","journal-title":"Cancer Res."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1158\/1535-7163.MCT-20-1026","article-title":"Novel and Highly Potent ATR Inhibitor M4344 Kills Cancer Cells With Replication Stress, and Enhances the Chemotherapeutic Activity of Widely Used DNA Damaging Agents","volume":"20","author":"Jo","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1158\/1535-7163.MCT-19-0019","article-title":"The Novel ATR Inhibitor BAY 1895344 Is Efficacious as Monotherapy and Combined with DNA Damage-Inducing or Repair-Compromising Therapies in Preclinical Cancer Models","volume":"19","author":"Wengner","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1158\/2159-8290.CD-20-0868","article-title":"First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors","volume":"11","author":"Yap","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF00685833","article-title":"Enhancement of antitumor activity of mitomycin C in vitro and in vivo by UCN-01, a selective inhibitor of protein kinase C","volume":"32","author":"Akinaga","year":"1993","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1093\/jnci\/88.14.956","article-title":"UCN-01: A Potent Abrogator of G 2 Checkpoint Function in Cancer Cells With Disrupted p53","volume":"88","author":"Wang","year":"1996","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_210","first-page":"4029","article-title":"Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-01) in human cancer cell lines, possibly influenced by p53 function","volume":"57","author":"Shao","year":"1997","journal-title":"Cancer Res."},{"key":"ref_211","first-page":"791","article-title":"Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor","volume":"2","author":"Bunch","year":"1996","journal-title":"Clin. Cancer Res."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"5650","DOI":"10.1158\/1078-0432.CCR-12-1322","article-title":"CCT244747 is a novel potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs","volume":"18","author":"Walton","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1080\/15384047.2018.1472189","article-title":"The CHK1 inhibitor SRA737 synergizes with PARP1 inhibitors to kill carcinoma cells","volume":"19","author":"Booth","year":"2018","journal-title":"Cancer Biol. Ther."},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Kristeleit, R., Plummer, R., Jones, R., Carter, L., Blagden, S., Sarker, D., Arkenau, T., Evans, T.R.J., Danson, S., and Symeonides, S.N. (2023). A Phase 1\/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer. Br. J. Cancer, In Press.","DOI":"10.1038\/s41416-023-02279-x"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1158\/1078-0432.CCR-22-2074","article-title":"A Phase I\/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer","volume":"29","author":"Jones","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1158\/1535-7163.MCT-14-1037","article-title":"LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms","volume":"14","author":"King","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13058-019-1192-2","article-title":"Prexasertib treatment induces homologous recombination deficiency and synergizes with olaparib in triple-negative breast cancer cells","volume":"21","author":"Mani","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"111026","DOI":"10.18632\/oncotarget.22195","article-title":"Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild type high-grade serous ovarian cancer","volume":"8","author":"Brill","year":"2017","journal-title":"Oncotarget"},{"key":"ref_219","first-page":"473","article-title":"Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in gastric cancer","volume":"7","author":"Yin","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.jtho.2019.01.028","article-title":"Checkpoint Kinase 1 Inhibition Enhances Cisplatin Cytotoxicity and Overcomes Cisplatin Resistance in SCLC by Promoting Mitotic Cell Death","volume":"14","author":"Hsu","year":"2019","journal-title":"J. Thorac. Oncol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1158\/1535-7163.MCT-09-0463","article-title":"Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents","volume":"8","author":"Hirai","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1158\/1535-7163.MCT-11-0529","article-title":"MK1775, a selective Wee1 inhibitor, shows single-agent antitumor activity against sarcoma cells","volume":"11","author":"Kreahling","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"15160","DOI":"10.1073\/pnas.1505283112","article-title":"A haploid genetic screen identifies the G1\/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity","volume":"112","author":"Heijink","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"4371","DOI":"10.1200\/JCO.2016.67.5991","article-title":"Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors","volume":"34","author":"Leijen","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"13004","DOI":"10.1021\/acs.jmedchem.1c01121","article-title":"Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer","volume":"64","author":"Huang","year":"2021","journal-title":"J. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10488\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:58:37Z","timestamp":1760126317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,22]]},"references-count":225,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310488"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310488","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,22]]}}}