{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:26:13Z","timestamp":1787286373759,"version":"build-2736575974"},"reference-count":167,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["1221162"],"award-info":[{"award-number":["1221162"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["152220002"],"award-info":[{"award-number":["152220002"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["3250447"],"award-info":[{"award-number":["3250447"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["21210962"],"award-info":[{"award-number":["21210962"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Replication and transcription share the DNA template and must be coordinated to preserve genome integrity. Although temporally organized across the cell cycle, essential transcriptional programs\u2014encoding replication machinery, canonical histones, and DNA repair factors\u2014operate concurrently with DNA synthesis during S phase. Transcription\u2013replication conflicts (TRCs) therefore constitute a recurrent endogenous source of replication stress (RS), particularly under hypertranscriptional or chromatin-constrained conditions. A frequent outcome of TRCs is the formation of R-loops\u2013RNA:DNA hybrids that can stall or collapse replication forks, leading to DNA damage. This review summarizes current evidence supporting a broader involvement of ERCC6\/CSB at the transcription\u2013replication interface beyond its established role in transcription-coupled repair. We discuss how ERCC6 participates in RNA polymerase II processing, chromatin remodeling, R-loop metabolism, replication fork protection, and repair pathway engagement following RS, operating through both its ATPase domain and intrinsically disordered regions. Conversely, in homologous recombination-deficient contexts, ERCC6 may favor mutagenic restart mechanisms, including break-induced replication; and recent evidence indicates that ERCC6 status influences cellular fate and the genomic distribution of stress-induced mutations, linking transcription-coupled repair with transcription-dependent mutagenesis. These observations support a model in which ERCC6 coordinates transcription-associated repair with RS responses, shaping genome maintenance and mutational outcomes, with implications for cancer and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms27167396","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:58:23Z","timestamp":1787126303000},"page":"7396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ERCC6 at the Transcription\u2013Replication Interface: Integration of Transcription-Coupled Repair with Replication Stress Responses"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0930-9529","authenticated-orcid":false,"given":"Evelyn","family":"Zambrano","sequence":"first","affiliation":[{"name":"Departamento de Oncolog\u00eda B\u00e1sico Cl\u00ednico, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Centro para la Prevenci\u00f3n y el Control del C\u00e1ncer (CECAN), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4653-8506","authenticated-orcid":false,"given":"Fernanda","family":"Morales","sequence":"additional","affiliation":[{"name":"Departamento de Oncolog\u00eda B\u00e1sico Cl\u00ednico, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Centro para la Prevenci\u00f3n y el Control del C\u00e1ncer (CECAN), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-0675","authenticated-orcid":false,"given":"Yanara A.","family":"Bernal","sequence":"additional","affiliation":[{"name":"Centro para la Prevenci\u00f3n y el Control del C\u00e1ncer (CECAN), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"School of Nursing, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-6623","authenticated-orcid":false,"given":"Katherine","family":"Marcelain","sequence":"additional","affiliation":[{"name":"Departamento de Oncolog\u00eda B\u00e1sico Cl\u00ednico, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Centro para la Prevenci\u00f3n y el Control del C\u00e1ncer (CECAN), Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1016\/j.molcel.2022.05.004","article-title":"Hallmarks of DNA Replication Stress","volume":"82","author":"Saxena","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ncb2897","article-title":"Causes and Consequences of Replication Stress","volume":"16","author":"Zeman","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41586-024-07517-7","article-title":"Single-Cell Nascent RNA Sequencing Unveils Coordinated Global Transcription","volume":"631","author":"Mahat","year":"2024","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1038\/s41467-020-17146-z","article-title":"E2F-Dependent Transcription Determines Replication Capacity and S Phase Length","volume":"11","author":"Pennycook","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112768","DOI":"10.1016\/j.celrep.2023.112768","article-title":"Cyclin E\/CDK2 and Feedback from Soluble Histone Protein Regulate the S Phase Burst of Histone Biosynthesis","volume":"42","author":"Armstrong","year":"2023","journal-title":"Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.dnarep.2015.03.007","article-title":"Cell Cycle Regulation of Human DNA Repair and Chromatin Remodeling Genes","volume":"30","author":"Mjelle","year":"2015","journal-title":"DNA Repair"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/j.celrep.2016.04.036","article-title":"Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage","volume":"15","author":"Bertoli","year":"2016","journal-title":"Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrc3916","article-title":"Replication Stress and Cancer","volume":"15","author":"Gaillard","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nrm.2016.88","article-title":"Transcription\u2013Replication Conflicts: How They Occur and How They Are Resolved","volume":"17","author":"Aguilera","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13087","DOI":"10.1038\/ncomms13087","article-title":"Increased Global Transcription Activity as a Mechanism of Replication Stress in Cancer","volume":"7","author":"Kotsantis","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.molcel.2011.10.013","article-title":"Collisions between Replication and Transcription Complexes Cause Common Fragile Site Instability at the Longest Human Genes","volume":"44","author":"Helmrich","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.1038\/s41467-019-13674-5","article-title":"Transcription-Mediated Organization of the Replication Initiation Program across Large Genes Sets Common Fragile Sites Genome-Wide","volume":"10","author":"Brison","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41580-019-0206-3","article-title":"Regulatory R-Loops as Facilitators of Gene Expression and Genome Stability","volume":"21","author":"Niehrs","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MCB.01251-07","article-title":"Mechanism of R-Loop Formation at Immunoglobulin Class Switch Sequences","volume":"28","author":"Roy","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.molcel.2019.01.024","article-title":"R-Loops as Cellular Regulators and Genomic Threats","volume":"73","author":"Crossley","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/s41580-022-00474-x","article-title":"Sources, Resolution and Physiological Relevance of R-Loops and RNA\u2013DNA Hybrids","volume":"23","author":"Petermann","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rinaldi, C., Pizzul, P., Longhese, M.P., and Bonetti, D. (2021). Sensing R-Loop-Associated DNA Damage to Safeguard Genome Stability. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.618157"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00412-023-00804-8","article-title":"Looping out of Control: R-Loops in Transcription-Replication Conflict","volume":"133","author":"Kumar","year":"2024","journal-title":"Chromosoma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.cell.2017.07.043","article-title":"Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses","volume":"170","author":"Hamperl","year":"2017","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1038\/s41467-020-15903-8","article-title":"The Cooperative Action of CSB, CSA, and UVSSA Target TFIIH to DNA Damage-Stalled RNA Polymerase II","volume":"11","author":"Mevissen","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103126","DOI":"10.1016\/j.dnarep.2021.103126","article-title":"Transcription-Coupled Nucleotide Excision Repair: New Insights Revealed by Genomic Approaches","volume":"103","author":"Duan","year":"2021","journal-title":"DNA Repair"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.1093\/nar\/gkae154","article-title":"CSB and SMARCAL1 Compete for RPA32 at Stalled Forks and Differentially Control the Fate of Stalled Forks in BRCA2-Deficient Cells","volume":"52","author":"Batenburg","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12836","DOI":"10.1093\/nar\/gkab1173","article-title":"Cockayne Syndrome Group B Protein Regulates Fork Restart, Fork Progression and MRE11-Dependent Fork Degradation in BRCA1\/2-Deficient Cells","volume":"49","author":"Batenburg","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41586-021-03906-4","article-title":"Structural Basis of Human Transcription\u2013DNA Repair Coupling","volume":"598","author":"Kokic","year":"2021","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1093\/nar\/gkz1114","article-title":"An R-Loop-Initiated CSB\u2013RAD52\u2013POLD3 Pathway Suppresses ROS-Induced Telomeric DNA Breaks","volume":"48","author":"Tan","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bilkis, R., Lake, R.J., and Fan, H.-Y. (2025). ATP-Dependent Chromatin Remodeler CSB Couples DNA Repair Pathways to Transcription with Implications for Cockayne Syndrome and Cancer Therapy. Cells, 14.","DOI":"10.3390\/cells14040239"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jeon, J., and Kang, T.-H. (2025). Transcription-Coupled Repair and R-Loop Crosstalk in Genome Stability. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083744"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.molcel.2014.10.020","article-title":"Transcription-Coupled Nucleotide Excision Repair Factors Promote R-Loop-Induced Genome Instability","volume":"56","author":"Sollier","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Batenburg, N.L., Walker, J.R., and Zhu, X.-D. (2023). CSB Regulates Pathway Choice in Response to DNA Replication Stress Induced by Camptothecin. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512419"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1038\/s41467-017-02114-x","article-title":"ATM and CDK2 Control Chromatin Remodeler CSB to Inhibit RIF1 in DSB Repair Pathway Choice","volume":"8","author":"Batenburg","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pardo, B., and Aguilera, A. (2012). Complex Chromosomal Rearrangements Mediated by Break-Induced Replication Involve Structure-Selective Endonucleases. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002979"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Deem, A., Keszthelyi, A., Blackgrove, T., Vayl, A., Coffey, B., Mathur, R., Chabes, A., and Malkova, A. (2011). Break-Induced Replication Is Highly Inaccurate. PLoS Biol., 9.","DOI":"10.1371\/journal.pbio.1000594"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.dnarep.2015.09.003","article-title":"Nucleotide Excision Repair in Humans","volume":"36","author":"Spivak","year":"2015","journal-title":"DNA Repair"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41580-022-00476-9","article-title":"Structural Insights into Nuclear Transcription by Eukaryotic DNA-Dependent RNA Polymerases","volume":"23","author":"Girbig","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105737","DOI":"10.1016\/j.jbc.2024.105737","article-title":"Transcription Elongation Mechanisms of RNA Polymerases I, II, and III and Their Therapeutic Implications","volume":"300","author":"Jacobs","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Barba-Aliaga, M., Alepuz, P., and P\u00e9rez-Ort\u00edn, J.E. (2021). Eukaryotic RNA Polymerases: The Many Ways to Transcribe a Gene. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.663209"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S1097-2765(02)00678-0","article-title":"CSB Is a Component of RNA Pol I Transcription","volume":"10","author":"Bradsher","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.molcel.2007.06.021","article-title":"Activation of RNA Polymerase I Transcription by Cockayne Syndrome Group B Protein and Histone Methyltransferase G9a","volume":"27","author":"Yuan","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Cho, I., Tsai, P.-F., Lake, R.J., Basheer, A., and Fan, H.-Y. (2013). ATP-Dependent Chromatin Remodeling by Cockayne Syndrome Protein B and NAP1-Like Histone Chaperones Is Required for Efficient Transcription-Coupled DNA Repair. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003407"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S1097-2765(00)80320-2","article-title":"Activation of P53 or Loss of the Cockayne Syndrome Group B Repair Protein Causes Metaphase Fragility of Human U1, U2, and 5S Genes","volume":"5","author":"Yu","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lalonde, M., Trauner, M., Werner, M., and Hamperl, S. (2021). Consequences and Resolution of Transcription\u2013Replication Conflicts. Life, 11.","DOI":"10.3390\/life11070637"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev-biochem-030222-115809","article-title":"Replication\u2013Transcription Conflicts: A Perpetual War on the Chromosome","volume":"93","author":"Browning","year":"2024","journal-title":"Annu. Rev. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.trecan.2021.04.006","article-title":"Hypertranscription and Replication Stress in Cancer","volume":"7","author":"Bowry","year":"2021","journal-title":"Trends Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41594-018-0171-0","article-title":"Transcription Shapes DNA Replication Initiation and Termination in Human Cells","volume":"26","author":"Chen","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"103872","DOI":"10.1016\/j.dnarep.2025.103872","article-title":"From Cooperation to Conflicts\u2014A Complicated Relationship between Transcription and Replication","volume":"152","author":"Musvi","year":"2025","journal-title":"DNA Repair"},{"key":"ref_46","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_47","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_48","doi-asserted-by":"crossref","first-page":"a012955","DOI":"10.1101\/cshperspect.a012955","article-title":"Dormant Origins, the Licensing Checkpoint, and the Response to Replicative Stresses","volume":"4","author":"McIntosh","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8956","DOI":"10.1073\/pnas.0803978105","article-title":"Excess MCM Proteins Protect Human Cells from Replicative Stress by Licensing Backup Origins of Replication","volume":"105","author":"Ibarra","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12929-021-00743-5","article-title":"Histone Dynamics during DNA Replication Stress","volume":"28","author":"Hsu","year":"2021","journal-title":"J. Biomed. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S1568-7864(02)00166-0","article-title":"Anti-Tumour Compounds Illudin S and Irofulven Induce DNA Lesions Ignored by Global Repair and Exclusively Processed by Transcription- and Replication-Coupled Repair Pathways","volume":"1","author":"Jaspers","year":"2002","journal-title":"DNA Repair"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/s41580-019-0169-4","article-title":"The DNA Damage Response to Transcription Stress","volume":"20","author":"Lans","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.1038\/s41467-022-31657-x","article-title":"The Mechanism of Replication Stalling and Recovery within Repetitive DNA","volume":"13","author":"Williams","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e114334","DOI":"10.15252\/embj.2023114334","article-title":"Replication-induced DNA Secondary Structures Drive Fork Uncoupling and Breakage","volume":"42","author":"Williams","year":"2023","journal-title":"EMBO J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00412-015-0545-6","article-title":"Linking Replication Stress with Heterochromatin Formation","volume":"125","author":"Nikolov","year":"2016","journal-title":"Chromosoma"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e2315596121","DOI":"10.1073\/pnas.2315596121","article-title":"Specialized Replication of Heterochromatin Domains Ensures Self-Templated Chromatin Assembly and Epigenetic Inheritance","volume":"121","author":"Nathanailidou","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1089\/ars.2014.5915","article-title":"Class I HDACs Affect DNA Replication, Repair, and Chromatin Structure: Implications for Cancer Therapy","volume":"23","author":"Stengel","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wells, C.E., Bhaskara, S., Stengel, K.R., Zhao, Y., Sirbu, B., Chagot, B., Cortez, D., Khabele, D., Chazin, W.J., and Cooper, A. (2013). Inhibition of Histone Deacetylase 3 Causes Replication Stress in Cutaneous T Cell Lymphoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068915"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1016\/j.molcel.2023.05.026","article-title":"Oncogenic IDH Mutations Increase Heterochromatin-Related Replication Stress without Impacting Homologous Recombination","volume":"83","author":"Schvartzman","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrm3822","article-title":"Understanding Nucleotide Excision Repair and Its Roles in Cancer and Ageing","volume":"15","author":"Marteijn","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.molcel.2013.08.007","article-title":"Enhanced Chromatin Dynamics by FACT Promotes Transcriptional Restart after UV-Induced DNA Damage","volume":"51","author":"Dinant","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"gkaf109","DOI":"10.1093\/nar\/gkaf109","article-title":"Transcription-Replication Conflicts Drive R-Loop-Dependent Nucleosome Eviction and Require DOT1L Activity for Transcription Recovery","volume":"53","author":"Werner","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Oksenych, V., Zhovmer, A., Ziani, S., Mari, P.-O., Eberova, J., Nardo, T., Stefanini, M., Giglia-Mari, G., Egly, J.-M., and Coin, F. (2013). Histone Methyltransferase DOT1L Drives Recovery of Gene Expression after a Genotoxic Attack. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003611"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"24163","DOI":"10.1074\/jbc.M003343200","article-title":"Transcription-Induced Cleavage of Immunoglobulin Switch Regions by Nucleotide Excision Repair Nucleases in Vitro","volume":"275","author":"Tian","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.molcel.2012.01.017","article-title":"R-Loop Formation Is a Distinctive Characteristic of Unmethylated Human CpG Island Promoters","volume":"45","author":"Ginno","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.molcel.2011.04.026","article-title":"Human Senataxin Resolves RNA\/DNA Hybrids Formed at Transcriptional Pause Sites to Promote Xrn2-Dependent Termination","volume":"42","author":"Proudfoot","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.molcel.2016.05.032","article-title":"Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals","volume":"63","author":"Sanz","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-S\u00e1nchez, M.S., Barroso, S., G\u00f3mez-Gonz\u00e1lez, B., Luna, R., and Aguilera, A. (2011). Genome Instability and Transcription Elongation Impairment in Human Cells Depleted of THO\/TREX. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002386"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Teng, Y., Yu, Y., Li, S., Huang, Y., Xu, D., Tao, X., and Fan, Y. (2021). Ultraviolet Radiation and Basal Cell Carcinoma: An Environmental Perspective. Front. Public Health, 9.","DOI":"10.3389\/fpubh.2021.666528"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1101\/gad.17010011","article-title":"R-Loop-Mediated Genomic Instability Is Caused by Impairment of Replication Fork Progression","volume":"25","author":"Gan","year":"2011","journal-title":"Genes Dev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5288","DOI":"10.1111\/febs.70104","article-title":"Transcription-coupled Repair: Tangled up in Convoluted Repair","volume":"292","author":"Pai","year":"2025","journal-title":"FEBS J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6031","DOI":"10.1038\/s41467-024-50298-w","article-title":"Cockayne Syndrome Linked to Elevated R-Loops Induced by Stalled RNA Polymerase II during Transcription Elongation","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"25486","DOI":"10.1073\/pnas.2013379117","article-title":"Cockayne Syndrome B Protein Acts as an ATP-Dependent Processivity Factor That Helps RNA Polymerase II Overcome Nucleosome Barriers","volume":"117","author":"Xu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1038\/s41467-018-06586-3","article-title":"ROS-Induced R Loops Trigger a Transcription-Coupled but BRCA1\/2-Independent Homologous Recombination Pathway through CSB","volume":"9","author":"Teng","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7776","DOI":"10.1038\/s41467-024-51784-x","article-title":"RAD52 Resolves Transcription-Replication Conflicts to Mitigate R-Loop Induced Genome Instability","volume":"15","author":"Jalan","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.molcel.2017.01.029","article-title":"Functions of Replication Protein A as a Sensor of R Loops and a Regulator of RNaseH1","volume":"65","author":"Nguyen","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"111749","DOI":"10.1016\/j.celrep.2022.111749","article-title":"Branchpoint Translocation by Fork Remodelers as a General Mechanism of R-Loop Removal","volume":"41","author":"Hodson","year":"2022","journal-title":"Cell Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1093\/nar\/gkad092","article-title":"Human Senataxin Is a Bona Fide R-Loop Resolving Enzyme and Transcription Termination Factor","volume":"51","author":"Hasanova","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1038\/s41467-020-17503-y","article-title":"BRD4 Prevents the Accumulation of R-Loops and Protects against Transcription\u2013Replication Collision Events and DNA Damage","volume":"11","author":"Lam","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Zambrano, E., Fierro, C., Morales, F., Manterola, M., Marin, A., Armisen, R., and Marcelain, K. (2026). Transcription-Coupled Repair Promotes the Retention of Mutations in Coding Regions During Replication Stress. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031154"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1007\/s00204-016-1820-x","article-title":"Transcription-Coupled Repair: An Update","volume":"90","author":"Spivak","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Walker, J.R., and Zhu, X.-D. (2022). Role of Cockayne Syndrome Group B Protein in Replication Stress: Implications for Cancer Therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810212"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1093\/nar\/gkab085","article-title":"Current and Emerging Roles of Cockayne Syndrome Group B (CSB) Protein","volume":"49","author":"Tiwari","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s41556-021-00688-9","article-title":"ELOF1 Is a Transcription-Coupled DNA Repair Factor That Directs RNA Polymerase II Ubiquitylation","volume":"23","author":"Nakazawa","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4740","DOI":"10.1016\/j.molcel.2024.10.030","article-title":"STK19 Drives Transcription-Coupled Repair by Stimulating Repair Complex Stability, RNA Pol II Ubiquitylation, and TFIIH Recruitment","volume":"84","author":"Ramadhin","year":"2024","journal-title":"Mol. Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7107","DOI":"10.1016\/j.cell.2024.10.018","article-title":"STK19 Facilitates the Clearance of Lesion-Stalled RNAPII during Transcription-Coupled DNA Repair","volume":"187","author":"Park","year":"2024","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7625","DOI":"10.1128\/MCB.25.17.7625-7636.2005","article-title":"Cooperation of the Cockayne Syndrome Group B Protein and Poly(ADP-Ribose) Polymerase 1 in the Response to Oxidative Stress","volume":"25","author":"Thorslund","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"17863","DOI":"10.1074\/jbc.RA118.004548","article-title":"Poly(ADP-Ribose) Polymerase 1 (PARP1) Promotes Oxidative Stress\u2013Induced Association of Cockayne Syndrome Group B Protein with Chromatin","volume":"293","author":"Boetefuer","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7342","DOI":"10.1093\/nar\/gkad515","article-title":"The CSB Chromatin Remodeler Regulates PARP1- and PARP2-Mediated Single-Strand Break Repair at Actively Transcribed DNA Regions","volume":"51","author":"Bilkis","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1093\/nar\/gkad256","article-title":"Requirement of Transcription-Coupled Nucleotide Excision Repair for the Removal of a Specific Type of Oxidatively Induced DNA Damage","volume":"51","author":"Sarmini","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7089","DOI":"10.1038\/s41467-024-51463-x","article-title":"Coordination of Transcription-Coupled Repair and Repair-Independent Release of Lesion-Stalled RNA Polymerase II","volume":"15","author":"Zhu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9596","DOI":"10.1093\/nar\/gkae618","article-title":"Differential Processing of RNA Polymerase II at DNA Damage Correlates with Transcription-Coupled Repair Syndrome Severity","volume":"52","author":"Steurer","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e2404383121","DOI":"10.1073\/pnas.2404383121","article-title":"The ARK2N\u2013CK2 Complex Initiates Transcription-Coupled Repair through Enhancing the Interaction of CSB with Lesion-Stalled RNAPII","volume":"121","author":"Luo","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e2425178122","DOI":"10.1073\/pnas.2425178122","article-title":"Evidence That ARK2N Is Not a Core Factor in Transcription-Coupled DNA Repair","volume":"122","author":"Brussee","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"20988","DOI":"10.1021\/jacs.1c10745","article-title":"Cockayne Syndrome B Protein Selectively Resolves and Interact with Intermolecular DNA G-Quadruplex Structures","volume":"143","author":"Liano","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Spyropoulou, Z., Papaspyropoulos, A., Lagopati, N., Myrianthopoulos, V., Georgakilas, A.G., Fousteri, M., Kotsinas, A., and Gorgoulis, V.G. (2021). Cockayne Syndrome Group B (CSB): The Regulatory Framework Governing the Multifunctional Protein and Its Plausible Role in Cancer. Cells, 10.","DOI":"10.3390\/cells10040866"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"gkaf1007","DOI":"10.1093\/nar\/gkaf1007","article-title":"GQ-DNABERT Reveals GQ Proximal Enhancer\u2013Promoter Interactions Associated with Tissue-Specific Transcription","volume":"53","author":"Konovalov","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1021\/acs.accounts.4c00574","article-title":"The Emerging Roles of Multimolecular G-Quadruplexes in Transcriptional Regulation and Chromatin Organization","volume":"57","author":"Antariksa","year":"2024","journal-title":"Acc. Chem. Res."},{"key":"ref_99","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_100","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1083\/jcb.201104003","article-title":"Mus81-Mediated DNA Cleavage Resolves Replication Forks Stalled by Topoisomerase I\u2013DNA Complexes","volume":"195","author":"Regairaz","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4009","DOI":"10.1007\/s00018-013-1307-3","article-title":"Checkpoint Kinase 1 in DNA Damage Response and Cell Cycle Regulation","volume":"70","author":"Patil","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"102313","DOI":"10.1016\/j.isci.2021.102313","article-title":"Replication-Stress-Associated DSBs Induced by Ionizing Radiation Risk Genomic Destabilization and Associated Clonal Evolution","volume":"24","author":"Matsuno","year":"2021","journal-title":"iScience"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Wilhelm, T., Ragu, S., Magdalou, I., Machon, C., Dardillac, E., T\u00e9cher, H., Guitton, J., Debatisse, M., and Lopez, B.S. (2016). Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006007"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"103354","DOI":"10.1016\/j.dnarep.2022.103354","article-title":"Cockayne Syndrome Group B Protein Uses Its DNA Translocase Activity to Promote Mitotic DNA Synthesis","volume":"116","author":"Cui","year":"2022","journal-title":"DNA Repair"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1093\/nar\/gkt1412","article-title":"Persistently Stalled Replication Forks Inhibit Nucleotide Excision Repair in Trans by Sequestering Replication Protein A","volume":"42","author":"Moser","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Stern, H.R., Sefcikova, J., Chaparro, V.E., and Beuning, P.J. (2019). Mammalian DNA Polymerase Kappa Activity and Specificity. Molecules, 24.","DOI":"10.3390\/molecules24152805"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"27566","DOI":"10.1073\/pnas.2014176117","article-title":"Polymerase \u03b4 Promotes Chromosomal Rearrangements and Imprecise Double-Strand Break Repair","volume":"117","author":"Layer","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.1038\/s41388-021-02032-9","article-title":"Unravelling Roles of Error-Prone DNA Polymerases in Shaping Cancer Genomes","volume":"40","author":"Vaziri","year":"2021","journal-title":"Oncogene"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev-biochem-052621-091205","article-title":"Transcription-Coupled Nucleotide Excision Repair and the Transcriptional Response to UV-Induced DNA Damage","volume":"92","author":"Olthof","year":"2023","journal-title":"Annu. Rev. Biochem."},{"key":"ref_110","first-page":"5","article-title":"Double Strand Break Repair Functions of Histone H2AX","volume":"750","author":"Scully","year":"2013","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"10614","DOI":"10.1093\/nar\/gkx715","article-title":"H2AX Facilitates Classical Non-Homologous End Joining at the Expense of Limited Nucleotide Loss at Repair Junctions","volume":"45","author":"Feng","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1038\/s41467-020-19502-5","article-title":"CHD7 and 53BP1 Regulate Distinct Pathways for the Re-Ligation of DNA Double-Strand Breaks","volume":"11","author":"Rother","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Sishc, B., and Davis, A. (2017). The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer. Cancers, 9.","DOI":"10.3390\/cancers9070081"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1126\/science.1243211","article-title":"Break-Induced Replication Repair of Damaged Forks Induces Genomic Duplications in Human Cells","volume":"343","author":"Costantino","year":"2014","journal-title":"Science"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.celrep.2013.03.004","article-title":"Suppression of Nucleotide Metabolism Underlies the Establishment and Maintenance of Oncogene-Induced Senescence","volume":"3","author":"Aird","year":"2013","journal-title":"Cell Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ajpath.2012.09.011","article-title":"Depletion of Deoxyribonucleotide Pools Is an Endogenous Source of DNA Damage in Cells Undergoing Oncogene-Induced Senescence","volume":"182","author":"Mannava","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.cell.2011.03.044","article-title":"Nucleotide Deficiency Promotes Genomic Instability in Early Stages of Cancer Development","volume":"145","author":"Bester","year":"2011","journal-title":"Cell"},{"key":"ref_118","first-page":"45","article-title":"Transcriptional De-Repression and Mfd Are Mutagenic in Stressed Bacillus Subtilis Cells","volume":"21","author":"Martin","year":"2011","journal-title":"J. Mol. Microbiol. Biotechnol."},{"key":"ref_119","first-page":"E1096","article-title":"An Underlying Mechanism for the Increased Mutagenesis of Lagging-Strand Genes in Bacillus subtilis","volume":"112","author":"Samadpour","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Han, J., Sahin, O., Barton, Y.-W., and Zhang, Q. (2008). Key Role of Mfd in the Development of Fluoroquinolone Resistance in Campylobacter Jejuni. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000083"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.molcel.2018.10.015","article-title":"Inhibiting the Evolution of Antibiotic Resistance","volume":"73","author":"Ragheb","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Gu, L., Hickey, R.J., and Malkas, L.H. (2023). Therapeutic Targeting of DNA Replication Stress in Cancer. Genes, 14.","DOI":"10.3390\/genes14071346"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41573-022-00558-5","article-title":"Targeting Replication Stress in Cancer Therapy","volume":"22","author":"Chowdhury","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Nickoloff, J.A., Jaiswal, A.S., Sharma, N., Williamson, E.A., Tran, M.T., Arris, D., Yang, M., and Hromas, R. (2023). Cellular Responses to Widespread DNA Replication Stress. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316903"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"R435","DOI":"10.1016\/j.cub.2014.04.012","article-title":"DNA Replication and Oncogene-Induced Replicative Stress","volume":"24","author":"Hills","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-012414-040424","article-title":"DNA Replication Stress as a Hallmark of Cancer","volume":"10","author":"Macheret","year":"2015","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.dnarep.2013.01.008","article-title":"The CSB Repair Factor Is Overexpressed in Cancer Cells, Increases Apoptotic Resistance, and Promotes Tumor Growth","volume":"12","author":"Caputo","year":"2013","journal-title":"DNA Repair"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.trecan.2018.01.005","article-title":"CSB: An Emerging Actionable Target for Cancer Therapy","volume":"4","author":"Balzerano","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1038\/s41388-020-1280-x","article-title":"Somatic Mutations in the DNA Repairome in Prostate Cancers in African Americans and Caucasians","volume":"39","author":"Yadav","year":"2020","journal-title":"Oncogene"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Ogundepo, O., and De Benedetti, A. (2026). Studies on the Functionality of the TC-NER ERCC6-M1097V Protein Variant Frequently Found in Louisiana Patients with PCa upon UV Damage. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1679379"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Kovalenko, T.F., Abdurazakov, A., Antipova, N.V., Shakhparonov, M.I., and Pavlyukov, M.S. (2025). R-Loops as a Trigger for Intra- and Extrachromosomal DNA Amplification in Cancer. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1647255"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41586-024-07802-5","article-title":"Enhancing Transcription\u2013Replication Conflict Targets ecDNA-Positive Cancers","volume":"635","author":"Tang","year":"2024","journal-title":"Nature"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"104710","DOI":"10.1016\/j.critrevonc.2025.104710","article-title":"WEE1 Inhibition in Cancer Therapy: Mechanisms, Synergies, Preclinical Insights, and Clinical Trials","volume":"211","author":"Thangaretnam","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2500632","DOI":"10.1002\/advs.202500632","article-title":"A Dual Approach with Organoid and CRISPR Screening Reveals ERCC6 as a Determinant of Cisplatin Resistance in Osteosarcoma","volume":"12","author":"Xu","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Musia\u0142ek, M.W., and Rybaczek, D. (2021). Hydroxyurea\u2014The Good, the Bad and the Ugly. Genes, 12.","DOI":"10.3390\/genes12071096"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41698-025-01166-3","article-title":"KRAS-Targeted Therapies in Colorectal Cancer: A Systematic Analysis of Mutations, Inhibitors, and Clinical Trials","volume":"9","author":"Mulet","year":"2025","journal-title":"npj Precis. Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"100963","DOI":"10.1016\/j.drup.2023.100963","article-title":"Targeting Myc-Driven Stress Addiction in Colorectal Cancer","volume":"69","author":"Saeed","year":"2023","journal-title":"Drug Resist. Updates"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.pccm.2023.07.001","article-title":"Role of C-Myc in Lung Cancer: Progress, Challenges, and Prospects","volume":"1","author":"Wallbillich","year":"2023","journal-title":"Chin. Med. J. Pulm. Crit. Care Med."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Karimi, N., and Moghaddam, S.J. (2023). KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions. Cells, 12.","DOI":"10.3390\/cells12050749"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41698-025-01087-1","article-title":"Molecular Characterization and Prognostic Implications of KRAS Mutations in Pancreatic Cancer Patients: Insights from Multi-Cohort Analysis","volume":"9","author":"Jiang","year":"2025","journal-title":"npj Precis. Oncol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Curti, L., and Campaner, S. (2021). MYC-Induced Replicative Stress: A Double-Edged Sword for Cancer Development and Treatment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126168"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.62347\/RTVX8866","article-title":"Exploiting Replication Stress for Synthetic Lethality in MYC-Driven Cancers","volume":"15","author":"Zhang","year":"2025","journal-title":"Am. J. Cancer Res."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"T\u00e9cher, H., Kemiha, S., Aobuli, X., and Kolinjivadi, A.M. (2024). Oncogenic RAS in Cancers from the DNA Replication Stress and Senescence Perspective. Cancers, 16.","DOI":"10.3390\/cancers16233993"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1053\/j.gastro.2025.02.038","article-title":"Therapeutic Targeting of Oncogene-Induced Transcription-Replication Conflicts in Pancreatic Ductal Adenocarcinoma","volume":"169","author":"Smith","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"12946","DOI":"10.1074\/jbc.RA120.013726","article-title":"Inhibition of the ATR Kinase Enhances 5-FU Sensitivity Independently of Nonhomologous End-Joining and Homologous Recombination Repair Pathways","volume":"295","author":"Ito","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4682","DOI":"10.1038\/onc.2017.40","article-title":"PARP Inhibitors Enhance Replication Stress and Cause Mitotic Catastrophe in MYCN-Dependent Neuroblastoma","volume":"36","author":"Colicchia","year":"2017","journal-title":"Oncogene"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1158\/1541-7786.MCR-17-0455","article-title":"PARP1 Trapping and DNA Replication Stress Enhance Radiosensitization with Combined WEE1 and PARP Inhibitors","volume":"16","author":"Parsels","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/s41416-024-02745-0","article-title":"ATR, CHK1 and WEE1 Inhibitors Cause Homologous Recombination Repair Deficiency to Induce Synthetic Lethality with PARP Inhibitors","volume":"131","author":"Smith","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_149","first-page":"189482","article-title":"Revisiting CHK1 and WEE1 Kinases as Therapeutic Targets in Cancer","volume":"1880","author":"Kumar","year":"2025","journal-title":"Biochim. Biophys. Acta BBA-Rev. Cancer"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1111\/cas.15845","article-title":"Emerging Strategies for Cancer Therapy by ATR Inhibitors","volume":"114","author":"Yano","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"e80207","DOI":"10.7554\/eLife.80207","article-title":"Oncogene Expression from Extrachromosomal DNA Is Driven by Copy Number Amplification and Does Not Require Spatial Clustering in Glioblastoma Stem Cells","volume":"11","author":"Purshouse","year":"2022","journal-title":"eLife"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"114711","DOI":"10.1016\/j.celrep.2024.114711","article-title":"Intercellular Extrachromosomal DNA Copy-Number Heterogeneity Drives Neuroblastoma Cell State Diversity","volume":"43","author":"Conrad","year":"2024","journal-title":"Cell Rep."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1158\/2767-9764.CRC-25-0058","article-title":"Histone Deacetylase Inhibitors Target DNA Replication Regulators and Replication Stress in Ewing Sarcoma Cells","volume":"5","author":"Koppenhafer","year":"2025","journal-title":"Cancer Res. Commun."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"a026831","DOI":"10.1101\/cshperspect.a026831","article-title":"HDACs and HDAC Inhibitors in Cancer Development and Therapy","volume":"6","author":"Li","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Byrd, A.K. (2012). Superfamily 2 Helicases. Front. Biosci., 17.","DOI":"10.2741\/4038"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"18566","DOI":"10.1073\/pnas.1420227112","article-title":"Regulation of the Rhp26ERCC6\/CSB Chromatin Remodeler by a Novel Conserved Leucine Latch Motif","volume":"111","author":"Wang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Caputo, M., Balzerano, A., Arisi, I., D\u2019Onofrio, M., Brandi, R., Bongiorni, S., Brancorsini, S., Frontini, M., and Proietti-De-Santis, L. (2017). CSB Ablation Induced Apoptosis Is Mediated by Increased Endoplasmic Reticulum Stress Response. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172399"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Nicolai, S., Filippi, S., Caputo, M., Cipak, L., Gregan, J., Ammerer, G., Frontini, M., Willems, D., Prantera, G., and Balajee, A.S. (2015). Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128558"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Haubold, M.K., Aquino, J.N.P., Rubin, S.R., Jones, I.K., Larsen, C.I.S., Pham, E., and Majumder, K. (2023). Genomes of the Autonomous Parvovirus Minute Virus of Mice Induce Replication Stress through RPA Exhaustion. PLoS Pathog., 19.","DOI":"10.1101\/2023.02.13.528428"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1038\/s41467-019-12064-1","article-title":"Typhoid Toxin Exhausts the RPA Response to DNA Replication Stress Driving Senescence and Salmonella Infection","volume":"10","author":"Ibler","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e01012-17","DOI":"10.1128\/JVI.01012-17","article-title":"Impact of Replication Stress in Human Papillomavirus Pathogenesis","volume":"93","author":"Moody","year":"2019","journal-title":"J. Virol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"8981","DOI":"10.1128\/JVI.00541-11","article-title":"The Papillomavirus E1 Helicase Activates a Cellular DNA Damage Response in Viral Replication Foci","volume":"85","author":"Sakakibara","year":"2011","journal-title":"J. Virol."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Saladino, N., and Salamango, D.J. (2024). Wielding a Double-Edged Sword: Viruses Exploit Host DNA Repair Systems to Facilitate Replication While Bypassing Immune Activation. Front. Virol., 4.","DOI":"10.3389\/fviro.2024.1410258"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1084\/jem.20180139","article-title":"The cGAS\u2013cGAMP\u2013STING Pathway Connects DNA Damage to Inflammation, Senescence, and Cancer","volume":"215","author":"Li","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41556-023-01343-1","article-title":"Mitochondrial DNA Replication Stress Triggers a Pro-Inflammatory Endosomal Pathway of Nucleoid Disposal","volume":"26","author":"Newman","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00018-024-05380-3","article-title":"R-Loops and Impaired Autophagy Trigger cGAS-Dependent Inflammation via Micronuclei Formation in Senataxin-Deficient Cells","volume":"81","author":"Zannini","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e2424666122","DOI":"10.1073\/pnas.2424666122","article-title":"A Noncanonical cGAS\u2013STING Pathway Drives Cellular and Organismal Aging","volume":"122","author":"Silva","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:16:25Z","timestamp":1787285785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":167,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167396"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167396","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}