{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:37:10Z","timestamp":1787567830859,"version":"build-2736575974"},"reference-count":65,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004520","name":"Tokyo Tech Academy for Co-creative Education of Environment and Energy Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20J13601"],"award-info":[{"award-number":["JP20J13601"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004051","name":"Kato Memorial Bioscience Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005118","name":"Japan Atomic Energy Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005118","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006530","name":"Chubu Electric Power Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004520","name":"Tokyo Tech Academy for Leadership","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K12369"],"award-info":[{"award-number":["JP22K12369"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15H02817"],"award-info":[{"award-number":["JP15H02817"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K20042"],"award-info":[{"award-number":["JP17K20042"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H04334"],"award-info":[{"award-number":["JP20H04334"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18K11642"],"award-info":[{"award-number":["JP18K11642"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Radiation Effects Association"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,11]]},"abstract":"<jats:p>Polynucleotide kinase phosphatase (PNKP) has enzymatic activities as 3\u2032-phosphatase and 5\u2032-kinase of DNA ends to promote DNA ligation and repair. Here, we show that cyclin-dependent kinases (CDKs) regulate the phosphorylation of threonine 118 (T118) in PNKP. This phosphorylation allows recruitment to the gapped DNA structure found in single-strand DNA (ssDNA) nicks and\/or gaps between Okazaki fragments (OFs) during DNA replication. T118A (alanine)-substituted PNKP-expressing cells exhibited an accumulation of ssDNA gaps in S phase and accelerated replication fork progression. Furthermore, PNKP is involved in poly (ADP-ribose) polymerase 1 (PARP1)-dependent replication gap filling as part of a backup pathway in the absence of OFs ligation. Altogether, our data suggest that CDK-mediated PNKP phosphorylation at T118 is important for its recruitment to ssDNA gaps to proceed with OFs ligation and its backup repairs via the gap-filling pathway to maintain genome stability.<\/jats:p>","DOI":"10.7554\/elife.99217","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T05:15:13Z","timestamp":1741756513000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.99217","source":"Crossref","is-referenced-by-count":2,"title":["CDK-mediated phosphorylation of PNKP is required for end-processing of single-strand DNA gaps on Okazaki fragments and genome stability"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6725-9514","authenticated-orcid":true,"given":"Kaima","family":"Tsukada","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]},{"id":[{"id":"https:\/\/ror.org\/035b05819","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Chromosome Stability, Department of Cellular and Molecular Medicine, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Rikiya","family":"Imamura","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3389-4007","authenticated-orcid":true,"given":"Tomoko","family":"Miyake","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Kotaro","family":"Saikawa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Mizuki","family":"Saito","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Naoya","family":"Kase","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Lingyan","family":"Fu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4313-9945","authenticated-orcid":true,"given":"Masamichi","family":"Ishiai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0025ww868","id-type":"ROR","asserted-by":"publisher"}],"name":"National Cancer Center Research Institute","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0758-290X","authenticated-orcid":true,"given":"Yoshihisa","family":"Matsumoto","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1980-9187","authenticated-orcid":true,"given":"Mikio","family":"Shimada","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dqf9946","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo","place":["Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237682","type":"journal-article","article-title":"Mutational survivorship bias: the case of PNKP","volume":"15","author":"Berm\u00fadez-Guzm\u00e1n","year":"2020","journal-title":"PLOS ONE"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","type":"journal-article","article-title":"ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response","volume":"66","author":"Blackford","year":"2017","journal-title":"Molecular Cell"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.ajhg.2015.01.005","type":"journal-article","article-title":"Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4","volume":"96","author":"Bras","year":"2015","journal-title":"American Journal of Human Genetics"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"4653","DOI":"10.1128\/MCB.00677-09","type":"journal-article","article-title":"DNA 3\u2019-phosphatase activity is critical for rapid global rates of single-strand break repair following oxidative stress","volume":"29","author":"Breslin","year":"2009","journal-title":"Molecular and Cellular Biology"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"4351","DOI":"10.1002\/j.1460-2075.1991.tb05013.x","type":"journal-article","article-title":"Emetine allows identification of origins of mammalian DNA replication by imbalanced DNA synthesis, not through conservative nucleosome segregation","volume":"10","author":"Burhans","year":"1991","journal-title":"The EMBO Journal"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.dnarep.2018.05.002","type":"journal-article","article-title":"Persistent 3\u2019-phosphate termini and increased cytotoxicity of radiomimetic DNA double-strand breaks in cells lacking polynucleotide kinase\/phosphatase despite presence of an alternative 3\u2019-phosphatase","volume":"68","author":"Chalasani","year":"2018","journal-title":"DNA Repair"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1093\/emboj\/21.11.2827","type":"journal-article","article-title":"Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining","volume":"21","author":"Chappell","year":"2002","journal-title":"The EMBO Journal"},{"key":"bib8","doi-asserted-by":"publisher","DOI":"10.1038\/srep24356","type":"journal-article","article-title":"CRISPR-Cas9(D10A) nickase-based genotypic and phenotypic screening to enhance genome editing","volume":"6","author":"Chiang","year":"2016","journal-title":"Scientific Reports"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"3128","DOI":"10.1016\/j.molcel.2021.06.011","type":"journal-article","article-title":"Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency","volume":"81","author":"Cong","year":"2021","journal-title":"Molecular Cell"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"21022","DOI":"10.1073\/pnas.1112036108","type":"journal-article","article-title":"Structural basis for the phosphatase activity of polynucleotide kinase\/phosphatase on single- and double-stranded DNA substrates","volume":"108","author":"Coquelle","year":"2011","journal-title":"PNAS"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1126\/science.286.5442.1162","type":"journal-article","article-title":"Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks","volume":"286","author":"Cortez","year":"1999","journal-title":"Science"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1126\/science.1065521","type":"journal-article","article-title":"ATR and ATRIP: partners in checkpoint signaling","volume":"294","author":"Cortez","year":"2001","journal-title":"Science"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1016\/j.celrep.2019.08.041","type":"journal-article","article-title":"Dual processing of R-loops and topoisomerase I induces transcription-dependent DNA double-strand breaks","volume":"28","author":"Cristini","year":"2019","journal-title":"Cell Reports"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1093\/nar\/gkl275","type":"journal-article","article-title":"The phosphatase activity of mammalian polynucleotide kinase takes precedence over its kinase activity in repair of single strand breaks","volume":"34","author":"Dobson","year":"2006","journal-title":"Nucleic Acids Research"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-1-4939-1680-1_10","type":"journal-article","article-title":"Purification of proteins on newly synthesized DNA using iPOND","volume":"1228","author":"Dungrawala","year":"2015","journal-title":"Methods in Molecular Biology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1038\/nchembio.2148","type":"journal-article","article-title":"Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site","volume":"12","author":"Exell","year":"2016","journal-title":"Nature Chemical Biology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"7739","DOI":"10.1158\/0008-5472.CAN-09-1805","type":"journal-article","article-title":"Identification of a small molecule inhibitor of the human DNA repair enzyme polynucleotide kinase\/phosphatase","volume":"69","author":"Freschauf","year":"2009","journal-title":"Cancer Research"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1091\/mbc.e06-12-1092","type":"journal-article","article-title":"Specialized roles of the two mitotic cyclins in somatic cells: cyclin A as an activator of M phase-promoting factor","volume":"18","author":"Fung","year":"2007","journal-title":"Molecular Biology of the Cell"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1016\/j.molcel.2020.12.010","type":"journal-article","article-title":"CARM1 regulates replication fork speed and stress response by stimulating PARP1","volume":"81","author":"Genois","year":"2021","journal-title":"Molecular Cell"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.molcel.2018.06.004","type":"journal-article","article-title":"The importance of poly(ADP-ribose) polymerase as a sensor of unligated okazaki fragments during DNA replication","volume":"71","author":"Hanzlikova","year":"2018","journal-title":"Molecular Cell"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/sj.emboj.7600554","type":"journal-article","article-title":"The structure of cyclin E1\/CDK2: implications for CDK2 activation and CDK2-independent roles","volume":"24","author":"Honda","year":"2005","journal-title":"The EMBO Journal"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"D512","DOI":"10.1093\/nar\/gku1267","type":"journal-article","article-title":"PhosphoSitePlus, 2014: mutations, PTMs and recalibrations","volume":"43","author":"Hornbeck","year":"2015","journal-title":"Nucleic Acids Research"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"24176","DOI":"10.1074\/jbc.274.34.24176","type":"journal-article","article-title":"Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3\u2019-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage","volume":"274","author":"Jilani","year":"1999","journal-title":"The Journal of Biological Chemistry"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000320","type":"journal-article","article-title":"Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ","volume":"5","author":"Kalasova","year":"2019","journal-title":"Neurology. Genetics"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"6672","DOI":"10.1093\/nar\/gkaa489","type":"journal-article","article-title":"Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair","volume":"48","author":"Kalasova","year":"2020","journal-title":"Nucleic Acids Research"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1269\/jrr.09146","type":"journal-article","article-title":"Radiation-induced XRCC4 association with chromatin DNA analyzed by biochemical fractionation","volume":"51","author":"Kamdar","year":"2010","journal-title":"Journal of Radiation Research"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"24187","DOI":"10.1074\/jbc.274.34.24187","type":"journal-article","article-title":"Molecular characterization of a human DNA kinase","volume":"274","author":"Karimi-Busheri","year":"1999","journal-title":"The Journal of Biological Chemistry"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1126\/science.1150034","type":"journal-article","article-title":"Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase","volume":"318","author":"Kolas","year":"2007","journal-title":"Science"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"16895","DOI":"10.1074\/jbc.R400006200","type":"journal-article","article-title":"DNA replication fidelity","volume":"279","author":"Kunkel","year":"2004","journal-title":"The Journal of Biological Chemistry"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/0042-6822(73)90059-7","type":"journal-article","article-title":"DNA replication in SV40-infected cells. IX. The inhibition of a gap-filling step during discontinuous synthesis of SV40 DNA","volume":"56","author":"Laipis","year":"1973","journal-title":"Virology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/s0092-8674(00)80752-7","type":"journal-article","article-title":"Substrate targeting in the ubiquitin system","volume":"97","author":"Laney","year":"1999","journal-title":"Cell"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.3390\/genes14010098","type":"journal-article","article-title":"Flap endonuclease 1 endonucleolytically processes RNA to resolve R-loops through DNA base excision repair","volume":"14","author":"Laverde","year":"2022","journal-title":"Genes"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010116","type":"journal-article","article-title":"DNA replication origins","volume":"5","author":"Leonard","year":"2013","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201560","type":"journal-article","article-title":"Emetine blocks DNA replication via proteosynthesis inhibition not by targeting Okazaki fragments","volume":"5","author":"Lukac","year":"2022","journal-title":"Life Science Alliance"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1128\/JVI.12.3.600-608.1973","type":"journal-article","article-title":"Hydroxyurea-induced accumulation of short fragments during polyoma DNA replication. I. Characterization of fragments","volume":"12","author":"Magnusson","year":"1973","journal-title":"Journal of Virology"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1128\/JVI.12.3.609-615.1973","type":"journal-article","article-title":"Hydroxyurea-induced accumulation of short fragments during polyoma DNA replication. II. Behavior during incubation of isolated nuclei","volume":"12","author":"Magnusson","year":"1973","journal-title":"Journal of Virology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"37619","DOI":"10.1074\/jbc.M109.058719","type":"journal-article","article-title":"Dual modes of interaction between XRCC4 and polynucleotide kinase\/phosphatase: implications for nonhomologous end joining","volume":"285","author":"Mani","year":"2010","journal-title":"The Journal of Biological Chemistry"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1074\/jbc.RA118.004262","type":"journal-article","article-title":"Domain analysis of PNKP-XRCC1 interactions: Influence of genetic variants of XRCC1","volume":"294","author":"Mani","year":"2019","journal-title":"The Journal of Biological Chemistry"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.115066","type":"journal-article","article-title":"PNKP safeguards stalled replication forks from nuclease-dependent degradation during replication stress","volume":"43","author":"Mashayekhi","year":"2024","journal-title":"Cell Reports"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/s41586-018-0261-5","type":"journal-article","article-title":"High speed of fork progression induces DNA replication stress and genomic instability","volume":"559","author":"Maya-Mendoza","year":"2018","journal-title":"Nature"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010108","type":"journal-article","article-title":"Principles and concepts of DNA replication in bacteria, archaea, and eukarya","volume":"5","author":"O\u2019Donnell","year":"2013","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1073\/pnas.59.2.598","type":"journal-article","article-title":"Mechanism of DNA chain growth. I. Possible discontinuity and unusual secondary structure of newly synthesized chains","volume":"59","author":"Okazaki","year":"1968","journal-title":"PNAS"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1002\/j.1460-2075.1992.tb05135.x","type":"journal-article","article-title":"Cyclin A is required at two points in the human cell cycle","volume":"11","author":"Pagano","year":"1992","journal-title":"The EMBO Journal"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"11404","DOI":"10.1093\/nar\/gks909","type":"journal-article","article-title":"Phosphorylation of PNKP by ATM prevents its proteasomal degradation and enhances resistance to oxidative stress","volume":"40","author":"Parsons","year":"2012","journal-title":"Nucleic Acids Research"},{"key":"bib45","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000030","type":"journal-article","article-title":"Mutation in PNKP presenting initially as axonal charcot-marie-tooth disease","volume":"1","author":"Pedroso","year":"2015","journal-title":"Neurology. Genetics"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nsmb.2258","type":"journal-article","article-title":"Topoisomerase I poisoning results in PARP-mediated replication fork reversal","volume":"19","author":"Ray Chaudhuri","year":"2012","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/nrm.2017.53","type":"journal-article","article-title":"The multifaceted roles of PARP1 in DNA repair and chromatin remodelling","volume":"18","author":"Ray Chaudhuri","year":"2017","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"6608","DOI":"10.1093\/nar\/gks318","type":"journal-article","article-title":"Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair","volume":"40","author":"Reynolds","year":"2012","journal-title":"Nucleic Acids Research"},{"key":"bib49","doi-asserted-by":"publisher","DOI":"10.3791\/3255","type":"journal-article","article-title":"Visualization of DNA replication in the vertebrate model system DT40 using the DNA fiber technique","volume":"e3255","author":"Schwab","year":"2011","journal-title":"Journal of Visualized Experiments"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/embor.2011.96","type":"journal-article","article-title":"ATM-mediated phosphorylation of polynucleotide kinase\/phosphatase is required for effective DNA double-strand break repair","volume":"12","author":"Segal-Raz","year":"2011","journal-title":"EMBO Reports"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/ng.526","type":"journal-article","article-title":"Mutations in PNKP cause microcephaly, seizures and defects in DNA repair","volume":"42","author":"Shen","year":"2010","journal-title":"Nature Genetics"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.15252\/embj.201591363","type":"journal-article","article-title":"Polynucleotide kinase-phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability","volume":"34","author":"Shimada","year":"2015","journal-title":"The EMBO Journal"},{"key":"bib53","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012930","type":"journal-article","article-title":"Regulating DNA replication in eukarya","volume":"5","author":"Siddiqui","year":"2013","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-021-04344-9","type":"journal-article","article-title":"CellProfiler 4: improvements in speed, utility and usability","volume":"22","author":"Stirling","year":"2021","journal-title":"BMC Bioinformatics"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1016\/j.cell.2016.11.034","type":"journal-article","article-title":"CDK substrate phosphorylation and ordering the cell cycle","volume":"167","author":"Swaffer","year":"2016","journal-title":"Cell"},{"key":"bib56","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16096-w","type":"journal-article","article-title":"Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly","volume":"11","author":"Thakar","year":"2020","journal-title":"Nature Communications"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1093\/jrr\/rraa128","type":"journal-article","article-title":"Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells","volume":"62","author":"Tsuchiya","year":"2021","journal-title":"Journal of Radiation Research"},{"key":"bib58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0239404","type":"journal-article","article-title":"Linker region is required for efficient nuclear localization of polynucleotide kinase phosphatase","volume":"15","author":"Tsukada","year":"2020","journal-title":"PLOS ONE"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2020.111727","type":"journal-article","article-title":"The FHA domain of PNKP is essential for its recruitment to DNA damage sites and maintenance of genome stability","volume":"822","author":"Tsukada","year":"2021","journal-title":"Mutation Research"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41594-022-00747-1","type":"journal-article","article-title":"PARP inhibition impedes the maturation of nascent DNA strands during DNA replication","volume":"29","author":"Vaitsiankova","year":"2022","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179278","type":"journal-article","article-title":"Small molecule inhibitors uncover synthetic genetic interactions of human flap endonuclease 1 (FEN1) with DNA damage response genes","volume":"12","author":"Ward","year":"2017","journal-title":"PLOS ONE"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1146\/annurev.biochem.66.1.61","type":"journal-article","article-title":"Replication protein A: A heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism","volume":"66","author":"Wold","year":"1997","journal-title":"Annual Review of Biochemistry"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/jmcb\/mjq048","type":"journal-article","article-title":"Okazaki fragment maturation: nucleases take centre stage","volume":"3","author":"Zheng","year":"2011","journal-title":"Journal of Molecular Cell Biology"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"9224","DOI":"10.1093\/nar\/gkr647","type":"journal-article","article-title":"Phosphorylation of polynucleotide kinase\/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage","volume":"39","author":"Zolner","year":"2011","journal-title":"Nucleic Acids Research"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1126\/science.1083430","type":"journal-article","article-title":"Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes","volume":"300","author":"Zou","year":"2003","journal-title":"Science"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/99217\/elife-99217-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/99217\/elife-99217-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/99217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:48:23Z","timestamp":1787564903000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/99217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,27]]},"references-count":65,"alternative-id":["10.7554\/eLife.99217"],"URL":"https:\/\/doi.org\/10.7554\/elife.99217","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.07.29.452278","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2021.07.29.452278","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.99217.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.99217.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.99217.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,27]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e99217"}}