{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:43:15Z","timestamp":1782963795942,"version":"3.54.5"},"reference-count":75,"publisher":"Cold Spring Harbor Laboratory","issue":"13-14","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM149683"],"award-info":[{"award-number":["R01GM149683"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"accepted":{"date-parts":[[2026,1,28]]},"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>By promoting replication through DNA lesions, translesion synthesis (TLS) DNA polymerases protect against chromosomal instability and tumorigenesis. However, it is not known whether TLS in mammalian cells operates in conjunction with the replisome or in postreplicational gaps and how that impacts genomic stability. Here we show that TLS in human cells operates in close coordination with the replisome and that ATR stabilizes the replisome at the stalled replication fork (RF). In ATR-inhibited cells, the CMG helicase and DNA synthesis components of the replisome disassemble from RFs stalled at DNA lesions, and the composition of TLS and DNA synthesis components and the ensuing TLS and replication mechanisms at the stalled RFs are altered drastically from those in ATR-proficient cells. These alterations include the lack of requirement for Rad18-dependent PCNA ubiquitination for TLS by Pol\u03b7 and primer synthesis by the newly identified PrimPol\u2013-PolA1\/PolA2 Pol\u03b1 complex. These results reveal the coupling of TLS to DNA replication, thus providing a means for protection against chromosome instability.<\/jats:p>","DOI":"10.1101\/gad.353474.125","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:15:19Z","timestamp":1778858119000},"page":"1059-1079","source":"Crossref","is-referenced-by-count":1,"title":["Coupling of translesion synthesis with the replisome stabilized at stalled replication forks by ATR"],"prefix":"10.1101","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1624-3635","authenticated-orcid":false,"given":"Jung-Hoon","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5703-9462","authenticated-orcid":false,"given":"Karthi","family":"Sellamuthu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-7123","authenticated-orcid":false,"given":"Robert E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9143-6261","authenticated-orcid":false,"given":"Louise","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-1444","authenticated-orcid":false,"given":"Satya","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"2026070108402228000_40.13-14.1059.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109981108"},{"key":"2026070108402228000_40.13-14.1059.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)01680-7"},{"key":"2026070108402228000_40.13-14.1059.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.10.019"},{"key":"2026070108402228000_40.13-14.1059.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04759-1"},{"key":"2026070108402228000_40.13-14.1059.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature09196"},{"key":"2026070108402228000_40.13-14.1059.6","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad507"},{"key":"2026070108402228000_40.13-14.1059.7","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1067403"},{"key":"2026070108402228000_40.13-14.1059.8","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg391"},{"key":"2026070108402228000_40.13-14.1059.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.15.4585"},{"key":"2026070108402228000_40.13-14.1059.10","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-08-0689"},{"key":"2026070108402228000_40.13-14.1059.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403410101"},{"key":"2026070108402228000_40.13-14.1059.12","doi-asserted-by":"publisher","DOI":"10.1038\/nature09097"},{"key":"2026070108402228000_40.13-14.1059.13","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-180"},{"key":"2026070108402228000_40.13-14.1059.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.01.007"},{"key":"2026070108402228000_40.13-14.1059.15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq046"},{"key":"2026070108402228000_40.13-14.1059.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.07.030"},{"key":"2026070108402228000_40.13-14.1059.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.09.018"},{"key":"2026070108402228000_40.13-14.1059.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.09.025"},{"key":"2026070108402228000_40.13-14.1059.19","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2851"},{"key":"2026070108402228000_40.13-14.1059.20","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201008076"},{"key":"2026070108402228000_40.13-14.1059.21","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E12-05-0339"},{"key":"2026070108402228000_40.13-14.1059.22","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E07-05-0500"},{"key":"2026070108402228000_40.13-14.1059.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5404.1001"},{"key":"2026070108402228000_40.13-14.1059.24","doi-asserted-by":"publisher","DOI":"10.1038\/35023030"},{"key":"2026070108402228000_40.13-14.1059.25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.7447"},{"key":"2026070108402228000_40.13-14.1059.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)08024-4"},{"key":"2026070108402228000_40.13-14.1059.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.05.038"},{"key":"2026070108402228000_40.13-14.1059.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104913"},{"key":"2026070108402228000_40.13-14.1059.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.028"},{"key":"2026070108402228000_40.13-14.1059.30","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku214"},{"key":"2026070108402228000_40.13-14.1059.31","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80361-5"},{"key":"2026070108402228000_40.13-14.1059.32","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.150"},{"key":"2026070108402228000_40.13-14.1059.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2009.06.011"},{"key":"2026070108402228000_40.13-14.1059.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)83733-4"},{"key":"2026070108402228000_40.13-14.1059.35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.758599"},{"key":"2026070108402228000_40.13-14.1059.36","doi-asserted-by":"publisher","DOI":"10.1038\/35087613"},{"key":"2026070108402228000_40.13-14.1059.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.11.015"},{"key":"2026070108402228000_40.13-14.1059.38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207199"},{"key":"2026070108402228000_40.13-14.1059.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-020-0476-7"},{"key":"2026070108402228000_40.13-14.1059.40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky230"},{"key":"2026070108402228000_40.13-14.1059.41","doi-asserted-by":"publisher","DOI":"10.1038\/21447"},{"key":"2026070108402228000_40.13-14.1059.42","doi-asserted-by":"publisher","DOI":"10.1126\/science.1140321"},{"key":"2026070108402228000_40.13-14.1059.43","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1883410"},{"key":"2026070108402228000_40.13-14.1059.44","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1118"},{"key":"2026070108402228000_40.13-14.1059.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2007.02.015"},{"key":"2026070108402228000_40.13-14.1059.46","doi-asserted-by":"publisher","DOI":"10.1110\/ps.035576.108"},{"key":"2026070108402228000_40.13-14.1059.47","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2017.03.019"},{"key":"2026070108402228000_40.13-14.1059.48","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1060"},{"key":"2026070108402228000_40.13-14.1059.49","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2010.8"},{"key":"2026070108402228000_40.13-14.1059.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.02.011"},{"key":"2026070108402228000_40.13-14.1059.51","doi-asserted-by":"publisher","DOI":"10.1038\/nature09104"},{"key":"2026070108402228000_40.13-14.1059.52","doi-asserted-by":"publisher","DOI":"10.1038\/nature10895"},{"key":"2026070108402228000_40.13-14.1059.53","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200905006"},{"key":"2026070108402228000_40.13-14.1059.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.10.016"},{"key":"2026070108402228000_40.13-14.1059.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.08.016"},{"key":"2026070108402228000_40.13-14.1059.56","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1065903"},{"key":"2026070108402228000_40.13-14.1059.57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007119"},{"key":"2026070108402228000_40.13-14.1059.58","doi-asserted-by":"publisher","DOI":"10.1038\/35087607"},{"key":"2026070108402228000_40.13-14.1059.59","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00169-2"},{"key":"2026070108402228000_40.13-14.1059.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.09.013"},{"key":"2026070108402228000_40.13-14.1059.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.09.015"},{"key":"2026070108402228000_40.13-14.1059.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.11.017"},{"key":"2026070108402228000_40.13-14.1059.63","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408026200"},{"key":"2026070108402228000_40.13-14.1059.64","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910121106"},{"key":"2026070108402228000_40.13-14.1059.65","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1872810"},{"key":"2026070108402228000_40.13-14.1059.66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007795107"},{"key":"2026070108402228000_40.13-14.1059.67","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204105109"},{"key":"2026070108402228000_40.13-14.1059.68","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.556977"},{"key":"2026070108402228000_40.13-14.1059.69","doi-asserted-by":"publisher","DOI":"10.1101\/gad.272229.115"},{"key":"2026070108402228000_40.13-14.1059.70","doi-asserted-by":"publisher","DOI":"10.1101\/gad.320531.118"},{"key":"2026070108402228000_40.13-14.1059.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.023"},{"key":"2026070108402228000_40.13-14.1059.72","doi-asserted-by":"publisher","DOI":"10.1101\/gad.348662.121"},{"key":"2026070108402228000_40.13-14.1059.73","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202000900"},{"key":"2026070108402228000_40.13-14.1059.74","doi-asserted-by":"publisher","DOI":"10.1101\/gad.351410.123"},{"key":"2026070108402228000_40.13-14.1059.75","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.106934"}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.353474.125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:41:24Z","timestamp":1782920484000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.353474.125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":75,"journal-issue":{"issue":"13-14","published-online":{"date-parts":[[2026,7,1]]},"published-print":{"date-parts":[[2026,7,1]]}},"alternative-id":["10.1101\/gad.353474.125"],"URL":"https:\/\/doi.org\/10.1101\/gad.353474.125","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}