{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:16:55Z","timestamp":1790749015571,"version":"4.1.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["102943\/Z\/13\/Z"],"award-info":[{"award-number":["102943\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UKRI | Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_12016\/13"],"award-info":[{"award-number":["MC_UU_12016\/13"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C578\/A24558"],"award-info":[{"award-number":["C578\/A24558"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C578\/A25669"],"award-info":[{"award-number":["C578\/A25669"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C5759\/A20971"],"award-info":[{"award-number":["C5759\/A20971"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K06611"],"award-info":[{"award-number":["JP19K06611"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K21423"],"award-info":[{"award-number":["JP20K21423"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/I001794\/1\/BB"],"award-info":[{"award-number":["BB\/I001794\/1\/BB"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Rep"],"published-print":{"date-parts":[[2021,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The eukaryotic replisome is disassembled in each cell cycle, dependent upon ubiquitylation of the CMG helicase. Studies of\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    ,\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    and\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    have revealed surprising evolutionary diversity in the ubiquitin ligases that control CMG ubiquitylation, but regulated disassembly of the mammalian replisome has yet to be explored. Here, we describe a model system for studying the ubiquitylation and chromatin extraction of the mammalian CMG replisome, based on mouse embryonic stem cells. We show that the ubiquitin ligase CUL2\n                    <jats:sup>LRR1<\/jats:sup>\n                    is required for ubiquitylation of the CMG-MCM7 subunit during S-phase, leading to disassembly by the p97 ATPase. Moreover, a second pathway of CMG disassembly is activated during mitosis, dependent upon the TRAIP ubiquitin ligase that is mutated in primordial dwarfism and mis-regulated in various cancers. These findings indicate that replisome disassembly in diverse metazoa is regulated by a conserved pair of ubiquitin ligases, distinct from those present in other eukaryotes.\n                  <\/jats:p>","DOI":"10.15252\/embr.202052164","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T16:16:33Z","timestamp":1613664993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["CUL2LRR1, TRAIP and p97 control CMG helicase disassembly in the mammalian cell cycle"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-7868","authenticated-orcid":false,"given":"Fabrizio","family":"Villa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1985-1668","authenticated-orcid":false,"given":"Ryo","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Ainsworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0194-4313","authenticated-orcid":false,"given":"Michael","family":"Lie-A-Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5630-2417","authenticated-orcid":false,"given":"Georges","family":"Lacaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-379X","authenticated-orcid":false,"given":"Karim PM","family":"Labib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"key":"BFEMBR202052164_CR1","doi-asserted-by":"crossref","first-page":"E5765","DOI":"10.1073\/pnas.1603241113","volume":"113","author":"M Al Mamun","year":"2016","unstructured":"Al Mamun M, Albergante L, Moreno A, Carrington JT, Blow JJ, Newman TJ (2016) Inevitability and containment of replication errors for eukaryotic genome lengths spanning megabase to gigabase. Proc Natl Acad Sci USA 113: E5765\u20135774","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202052164_CR2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.ccell.2015.10.002","volume":"28","author":"DJ Anderson","year":"2015","unstructured":"Anderson DJ, Le Moigne R, Djakovic S, Kumar B, Rice J, Wong S, Wang J, Yao B, Valle E, Kiss von Soly S et al (2015) Targeting the AAA ATPase p97 as an approach to treat cancer through disruption of protein homeostasis. Cancer Cell 28: 653\u2013665","journal-title":"Cancer Cell"},{"key":"BFEMBR202052164_CR3","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41586-020-2000-y","volume":"578","author":"K Baek","year":"2020","unstructured":"Baek K, Krist DT, Prabu JR, Hill S, Klugel M, Neumaier LM, von Gronau S, Kleiger G, Schulman BA (2020) NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly. Nature 578: 461\u2013466","journal-title":"Nature"},{"key":"BFEMBR202052164_CR4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/978-981-10-6955-0_10","volume":"1042","author":"L Bai","year":"2017","unstructured":"Bai L, Yuan Z, Sun J, Georgescu R, O'Donnell ME, Li H (2017) Architecture of the Saccharomyces cerevisiae replisome. Adv Exp Med Biol 1042: 207\u2013228","journal-title":"Adv Exp Med Biol"},{"key":"BFEMBR202052164_CR5","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1534\/genetics.115.186452","volume":"203","author":"SP Bell","year":"2016","unstructured":"Bell SP, Labib K (2016) Chromosome duplication in Saccharomyces cerevisiae. Genetics 203: 1027\u20131067","journal-title":"Genetics"},{"key":"BFEMBR202052164_CR6","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.molcel.2016.10.037","volume":"64","author":"R Bhowmick","year":"2016","unstructured":"Bhowmick R, Minocherhomji S, Hickson ID (2016) RAD52 facilitates mitotic DNA synthesis following replication stress. Mol Cell 64: 1117\u20131126","journal-title":"Mol Cell"},{"key":"BFEMBR202052164_CR7","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1083\/jcb.105.4.1549","volume":"105","author":"R Bravo","year":"1987","unstructured":"Bravo R, Macdonald-Bravo H (1987) Existence of two populations of cyclin\/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol 105: 1549\u20131554","journal-title":"J Cell Biol"},{"key":"BFEMBR202052164_CR8","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/S0962-8924(02)02352-8","volume":"12","author":"T Burdon","year":"2002","unstructured":"Burdon T, Smith A, Savatier P (2002) Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol 12: 432\u2013438","journal-title":"Trends Cell Biol"},{"key":"BFEMBR202052164_CR9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003375","volume":"9","author":"J Burger","year":"2013","unstructured":"Burger J, Merlet J, Tavernier N, Richaudeau B, Arnold A, Ciosk R, Bowerman B, Pintard L (2013) CRL2(LRR-1) E3-ligase regulates proliferation and progression through meiosis in the Caenorhabditis elegans germline. PLoS Genet 9: e1003375","journal-title":"PLoS Genet"},{"key":"BFEMBR202052164_CR10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev-biochem-061516-044709","volume":"86","author":"PMJ Burgers","year":"2017","unstructured":"Burgers PMJ, Kunkel TA (2017) Eukaryotic DNA replication fork. Annu Rev Biochem 86: 417\u2013438","journal-title":"Annu Rev Biochem"},{"key":"BFEMBR202052164_CR11","first-page":"5149","volume":"127","author":"C Chapard","year":"2014","unstructured":"Chapard C, Meraldi P, Gleich T, Bachmann D, Hohl D, Huber M (2014) TRAIP is a regulator of the spindle assembly checkpoint. J Cell Sci 127: 5149\u20135156","journal-title":"J Cell Sci"},{"key":"BFEMBR202052164_CR12","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.60371","volume":"9","author":"TD Deegan","year":"2020","unstructured":"Deegan TD, Mukherjee PP, Fujisawa R, Polo Rivera C, Labib K (2020) CMG helicase disassembly is controlled by replication fork DNA, replisome components and a ubiquitin threshold. eLife 9: e60371","journal-title":"eLife"},{"key":"BFEMBR202052164_CR13","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.molcel.2018.12.021","volume":"73","author":"L Deng","year":"2019","unstructured":"Deng L, Wu RA, Sonneville R, Kochenova OV, Labib K, Pellman D, Walter JC (2019) Mitotic CDK promotes replisome disassembly, fork breakage, and complex DNA rearrangements. Mol Cell 73: 915\u2013929","journal-title":"Mol Cell"},{"key":"BFEMBR202052164_CR14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature14887","volume":"525","author":"JM Dewar","year":"2015","unstructured":"Dewar JM, Budzowska M, Walter JC (2015) The mechanism of DNA replication termination in vertebrates. Nature 525: 345\u2013350","journal-title":"Nature"},{"key":"BFEMBR202052164_CR15","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1101\/gad.291799.116","volume":"31","author":"JM Dewar","year":"2017","unstructured":"Dewar JM, Low E, Mann M, Raschle M, Walter JC (2017) CRL2(Lrr1) promotes unloading of the vertebrate replisome from chromatin during replication termination. Genes Dev 31: 275\u2013290","journal-title":"Genes Dev"},{"key":"BFEMBR202052164_CR16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nature25787","volume":"555","author":"ME Douglas","year":"2018","unstructured":"Douglas ME, Ali FA, Costa A, Diffley JFX (2018) The mechanism of eukaryotic CMG helicase activation. Nature 555: 265\u2013268","journal-title":"Nature"},{"key":"BFEMBR202052164_CR17","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1021\/ja309802n","volume":"135","author":"R Ekkebus","year":"2013","unstructured":"Ekkebus R, van Kasteren SI, Kulathu Y, Scholten A, Berlin I, Geurink PP, de Jong A, Goerdayal S, Neefjes J, Heck AJ et al (2013) On terminal alkynes that can react with active-site cysteine nucleophiles in proteases. J Am Chem Soc 135: 2867\u20132870","journal-title":"J Am Chem Soc"},{"key":"BFEMBR202052164_CR18","doi-asserted-by":"crossref","first-page":"9350","DOI":"10.1128\/MCB.25.21.9350-9359.2005","volume":"25","author":"J Essers","year":"2005","unstructured":"Essers J, Theil AF, Baldeyron C, van Cappellen WA, Houtsmuller AB, Kanaar R, Vermeulen W (2005) Nuclear dynamics of PCNA in DNA replication and repair. Mol Cell Biol 25: 9350\u20139359","journal-title":"Mol Cell Biol"},{"key":"BFEMBR202052164_CR19","doi-asserted-by":"crossref","first-page":"20240","DOI":"10.1073\/pnas.0911500106","volume":"106","author":"C Evrin","year":"2009","unstructured":"Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C (2009) A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci USA 106: 20240\u201320245","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202052164_CR20","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.cell.2011.07.045","volume":"146","author":"YV Fu","year":"2011","unstructured":"Fu YV, Yardimci H, Long DT, Ho TV, Guainazzi A, Bermudez VP, Hurwitz J, van Oijen A, Scharer OD, Walter JC (2011) Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell 146: 931\u2013941","journal-title":"Cell"},{"key":"BFEMBR202052164_CR21","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1038\/emboj.2009.226","volume":"28","author":"A Gambus","year":"2009","unstructured":"Gambus A, van Deursen F, Polychronopoulos D, Foltman M, Jones RC, Edmondson RD, Calzada A, Labib K (2009) A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome. EMBO J 28: 2992\u20133004","journal-title":"EMBO J"},{"key":"BFEMBR202052164_CR22","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/ncb1382","volume":"8","author":"A Gambus","year":"2006","unstructured":"Gambus A, Jones RC, Sanchez-Diaz A, Kanemaki M, van Deursen F, Edmondson RD, Labib K (2006) GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat Cell Biol 8: 358\u2013366","journal-title":"Nat Cell Biol"},{"key":"BFEMBR202052164_CR23","doi-asserted-by":"crossref","first-page":"11855","DOI":"10.1074\/jbc.M110.199521","volume":"286","author":"A Gambus","year":"2011","unstructured":"Gambus A, Khoudoli GA, Jones RC, Blow JJ (2011) MCM2-7 form double hexamers at licensed origins in Xenopus egg extract. J Biol Chem 286: 11855\u201311864","journal-title":"J Biol Chem"},{"key":"BFEMBR202052164_CR24","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.cell.2019.03.034","volume":"177","author":"S Gasser","year":"2019","unstructured":"Gasser S (2019) Once and only once. Cell 177: 495\u2013498","journal-title":"Cell"},{"key":"BFEMBR202052164_CR25","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrc.2017.52","volume":"17","author":"TW Glover","year":"2017","unstructured":"Glover TW, Wilson TE, Arlt MF (2017) Fragile sites in cancer: more than meets the eye. Nat Rev Cancer 17: 489\u2013501","journal-title":"Nat Rev Cancer"},{"key":"BFEMBR202052164_CR26","first-page":"3305","volume":"41","author":"YG Han","year":"2019","unstructured":"Han YG, Yun M, Choi M, Lee SG, Kim H (2019) TRAIP regulates Histone H2B monoubiquitination in DNA damage response pathways. Oncol Rep 41: 3305\u20133312","journal-title":"Oncol Rep"},{"key":"BFEMBR202052164_CR27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/ng.3451","volume":"48","author":"ME Harley","year":"2016","unstructured":"Harley ME, Murina O, Leitch A, Higgs MR, Bicknell LS, Yigit G, Blackford AN, Zlatanou A, Mackenzie KJ, Reddy K et al (2016) TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Nat Genet 48: 36\u201343","journal-title":"Nat Genet"},{"key":"BFEMBR202052164_CR28","doi-asserted-by":"crossref","first-page":"R435","DOI":"10.1016\/j.cub.2014.04.012","volume":"24","author":"SA Hills","year":"2014","unstructured":"Hills SA, Diffley JF (2014) DNA replication and oncogene-induced replicative stress. Curr Biol 24: R435\u2013444","journal-title":"Curr Biol"},{"key":"BFEMBR202052164_CR29","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1083\/jcb.201506071","volume":"212","author":"S Hoffmann","year":"2016","unstructured":"Hoffmann S, Smedegaard S, Nakamura K, Mortuza GB, Raschle M, Ibanez de Opakua A, Oka Y, Feng Y, Blanco FJ, Mann M et al (2016) TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress. J Cell Biol 212: 63\u201375","journal-title":"J Cell Biol"},{"key":"BFEMBR202052164_CR30","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S1016-8478(23)25210-3","volume":"12","author":"LK Jang","year":"2001","unstructured":"Jang LK, Lee ZH, Kim HH, Hill JM, Kim JD, Kwon BS (2001) A novel leucine-rich repeat protein (LRR-1): potential involvement in 4\u20131BB-mediated signal transduction. Mol Cells 12: 304\u2013312","journal-title":"Mol Cells"},{"key":"BFEMBR202052164_CR31","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1101\/gad.1252404","volume":"18","author":"T Kamura","year":"2004","unstructured":"Kamura T, Maenaka K, Kotoshiba S, Matsumoto M, Kohda D, Conaway RC, Conaway JW, Nakayama KI (2004) VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev 18: 3055\u20133065","journal-title":"Genes Dev"},{"key":"BFEMBR202052164_CR32","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.molcel.2016.11.016","volume":"65","author":"CF Kurat","year":"2017","unstructured":"Kurat CF, Yeeles JT, Patel H, Early A, Diffley JF (2017) Chromatin controls DNA replication origin selection, lagging-strand synthesis, and replication fork rates. Mol Cell 65: 117\u2013130","journal-title":"Mol Cell"},{"key":"BFEMBR202052164_CR33","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1083\/jcb.149.2.271","volume":"149","author":"H Leonhardt","year":"2000","unstructured":"Leonhardt H, Rahn HP, Weinzierl P, Sporbert A, Cremer T, Zink D, Cardoso MC (2000) Dynamics of DNA replication factories in living cells. J Cell Biol 149: 271\u2013280","journal-title":"J Cell Biol"},{"key":"BFEMBR202052164_CR34","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.molcel.2019.10.005","volume":"77","author":"JS Lewis","year":"2020","unstructured":"Lewis JS, Spenkelink LM, Schauer GD, Yurieva O, Mueller SH, Natarajan V, Kaur G, Maher C, Kay C, O'Donnell ME et al (2020) Tunability of DNA polymerase stability during eukaryotic DNA replication. Mol Cell 77: 17\u201325","journal-title":"Mol Cell"},{"key":"BFEMBR202052164_CR35","doi-asserted-by":"crossref","first-page":"3014","DOI":"10.1093\/nar\/gkaa038","volume":"48","author":"N Li","year":"2020","unstructured":"Li N, Wang J, Wallace SS, Chen J, Zhou J, D'Andrea AD (2020) Cooperation of the NEIL3 and Fanconi anemia\/BRCA pathways in interstrand crosslink repair. Nucleic Acids Res 48: 3014\u20133028","journal-title":"Nucleic Acids Res"},{"key":"BFEMBR202052164_CR36","doi-asserted-by":"crossref","DOI":"10.1126\/science.1253596","volume":"346","author":"M Maric","year":"2014","unstructured":"Maric M, Maculins T, De Piccoli G, Labib K (2014) Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication. Science 346: 1253596","journal-title":"Science"},{"key":"BFEMBR202052164_CR37","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1016\/j.celrep.2017.03.020","volume":"18","author":"M Maric","year":"2017","unstructured":"Maric M, Mukherjee P, Tatham MH, Hay R, Labib K (2017) Ufd1-Npl4 recruit Cdc48 for disassembly of ubiquitylated CMG helicase at the end of chromosome replication. Cell Rep 18: 3033\u20133042","journal-title":"Cell Rep"},{"key":"BFEMBR202052164_CR38","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.30473","volume":"6","author":"JP Matson","year":"2017","unstructured":"Matson JP, Dumitru R, Coryell P, Baxley RM, Chen W, Twaroski K, Webber BR, Tolar J, Bielinsky AK, Purvis JE et al (2017) Rapid DNA replication origin licensing protects stem cell pluripotency. eLife 6: e30473","journal-title":"eLife"},{"key":"BFEMBR202052164_CR39","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1242\/dev.054866","volume":"137","author":"J Merlet","year":"2010","unstructured":"Merlet J, Burger J, Tavernier N, Richaudeau B, Gomes JE, Pintard L (2010) The CRL2LRR-1 ubiquitin ligase regulates cell cycle progression during C. elegans development. Development 137: 3857\u20133866","journal-title":"Development"},{"key":"BFEMBR202052164_CR40","doi-asserted-by":"crossref","first-page":"E5757","DOI":"10.1073\/pnas.1603252113","volume":"113","author":"A Moreno","year":"2016","unstructured":"Moreno A, Carrington JT, Albergante L, Al Mamun M, Haagensen EJ, Komseli ES, Gorgoulis VG, Newman TJ, Blow JJ (2016) Unreplicated DNA remaining from unperturbed S phases passes through mitosis for resolution in daughter cells. Proc Natl Acad Sci USA 113: E5757\u2013E5764","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202052164_CR41","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1126\/science.1253585","volume":"346","author":"SP Moreno","year":"2014","unstructured":"Moreno SP, Bailey R, Campion N, Herron S, Gambus A (2014) Polyubiquitylation drives replisome disassembly at the termination of DNA replication. Science 346: 477\u2013481","journal-title":"Science"},{"key":"BFEMBR202052164_CR42","doi-asserted-by":"crossref","first-page":"10236","DOI":"10.1073\/pnas.0602400103","volume":"103","author":"SE Moyer","year":"2006","unstructured":"Moyer SE, Lewis PW, Botchan MR (2006) Isolation of the Cdc45\/Mcm2-7\/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proc Natl Acad Sci USA 103: 10236\u201310241","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202052164_CR43","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1016\/j.celrep.2019.08.026","volume":"28","author":"PP Mukherjee","year":"2019","unstructured":"Mukherjee PP, Labib KPM (2019) In vitro reconstitution defines the minimal requirements for Cdc48-dependent disassembly of the CMG helicase in budding yeast. Cell Rep 28: 2777\u20132783","journal-title":"Cell Rep"},{"key":"BFEMBR202052164_CR44","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.bbrc.2007.09.103","volume":"363","author":"ES Park","year":"2007","unstructured":"Park ES, Choi S, Kim JM, Jeong Y, Choe J, Park CS, Choi Y, Rho J (2007) Early embryonic lethality caused by targeted disruption of the TRAF-interacting protein (TRIP) gene. Biochem Biophys Res Commun 363: 971\u2013977","journal-title":"Biochem Biophys Res Commun"},{"key":"BFEMBR202052164_CR45","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.tibs.2016.07.011","volume":"41","author":"L Pellegrini","year":"2016","unstructured":"Pellegrini L, Costa A (2016) New insights into the mechanism of DNA duplication by the eukaryotic replisome. Trends Biochem Sci 41: 859\u2013871","journal-title":"Trends Biochem Sci"},{"key":"BFEMBR202052164_CR46","volume":"2","author":"S Priego Moreno","year":"2019","unstructured":"Priego Moreno S, Jones RM, Poovathumkadavil D, Scaramuzza S, Gambus A (2019) Mitotic replisome disassembly depends on TRAIP ubiquitin ligase activity. Life Sc Alliance 2: e201900390","journal-title":"Life Sc Alliance"},{"key":"BFEMBR202052164_CR47","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/978-1-62703-761-7_17","volume":"1114","author":"NK Pyzocha","year":"2014","unstructured":"Pyzocha NK, Ran FA, Hsu PD, Zhang F (2014) RNA-guided genome editing of mammalian cells. Methods Mol Biol 1114: 269\u2013277","journal-title":"Methods Mol Biol"},{"key":"BFEMBR202052164_CR48","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.cell.2009.10.015","volume":"139","author":"D Remus","year":"2009","unstructured":"Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF (2009) Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell 139: 719\u2013730","journal-title":"Cell"},{"key":"BFEMBR202052164_CR49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1756-8935-8-3","volume":"8","author":"N Saksouk","year":"2015","unstructured":"Saksouk N, Simboeck E, Dejardin J (2015) Constitutive heterochromatin formation and transcription in mammals. Epigenetics Chromatin 8: 3","journal-title":"Epigenetics Chromatin"},{"key":"BFEMBR202052164_CR50","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1042\/BCJ20180883","volume":"476","author":"S Sarkar","year":"2019","unstructured":"Sarkar S, Behera AP, Borar P, Banka PA, Datta AB (2019) Designing active RNF4 monomers by introducing a tryptophan: avidity towards E2 approximately Ub conjugates dictates the activity of ubiquitin RING E3 ligases. Biochem J 476: 1465\u20131482","journal-title":"Biochem J"},{"key":"BFEMBR202052164_CR51","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.cub.2013.02.011","volume":"23","author":"S Sengupta","year":"2013","unstructured":"Sengupta S, van Deursen F, de Piccoli G, Labib K (2013) Dpb2 integrates the leading-strand DNA polymerase into the eukaryotic replisome. Curr Biol 23: 543\u2013552","journal-title":"Curr Biol"},{"key":"BFEMBR202052164_CR52","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0092-8674(00)80661-3","volume":"96","author":"K Shibahara","year":"1999","unstructured":"Shibahara K, Stillman B (1999) Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin. Cell 96: 575\u2013585","journal-title":"Cell"},{"key":"BFEMBR202052164_CR53","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.48686","volume":"8","author":"R Sonneville","year":"2019","unstructured":"Sonneville R, Bhowmick R, Hoffmann S, Mailand N, Hickson ID, Labib K (2019) TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication. eLife 8: e48686","journal-title":"eLife"},{"key":"BFEMBR202052164_CR54","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/ncb3500","volume":"19","author":"R Sonneville","year":"2017","unstructured":"Sonneville R, Moreno SP, Knebel A, Johnson C, Hastie CJ, Gartner A, Gambus A, Labib K (2017) CUL-2(LRR-1) and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis. Nat Cell Biol 19: 468\u2013479","journal-title":"Nat Cell Biol"},{"key":"BFEMBR202052164_CR55","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10463","volume":"7","author":"N Soo Lee","year":"2016","unstructured":"Soo Lee N, Jin Chung H, Kim HJ, Yun Lee S, Ji JH, Seo Y, Hun Han S, Choi M, Yun M, Lee SG et al (2016) TRAIP\/RNF206 is required for recruitment of RAP80 to sites of DNA damage. Nat Commun 7: 10463","journal-title":"Nat Commun"},{"key":"BFEMBR202052164_CR56","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nature07884","volume":"458","author":"TA Soucy","year":"2009","unstructured":"Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S et al (2009) An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458: 732\u2013736","journal-title":"Nature"},{"key":"BFEMBR202052164_CR57","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cell.2018.10.053","volume":"176","author":"JL Sparks","year":"2019","unstructured":"Sparks JL, Chistol G, Gao AO, Raschle M, Larsen NB, Mann M, Duxin JP, Walter JC (2019) The CMG helicase bypasses DNA-protein cross-links to facilitate their repair. Cell 176: 167\u2013181","journal-title":"Cell"},{"key":"BFEMBR202052164_CR58","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.devcel.2010.10.013","volume":"19","author":"NG Starostina","year":"2010","unstructured":"Starostina NG, Simpliciano JM, McGuirk MA, Kipreos ET (2010) CRL2(LRR-1) targets a CDK inhibitor for cell cycle control in C. elegans and actin-based motility regulation in human cells. Dev Cell 19: 753\u2013764","journal-title":"Dev Cell"},{"key":"BFEMBR202052164_CR59","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.stem.2017.09.004","volume":"21","author":"M Ter Huurne","year":"2017","unstructured":"Ter Huurne M, Chappell J, Dalton S, Stunnenberg HG (2017) Distinct cell-cycle control in two different states of mouse pluripotency. Cell Stem Cell 21: 449\u2013455","journal-title":"Cell Stem Cell"},{"key":"BFEMBR202052164_CR60","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.12.039","author":"KB Vrtis","year":"2021","unstructured":"Vrtis KB, Dewar JM, Chistol G, Wu RA, Graham TGW, Walter JC (2021) Single-strand DNA breaks cause replisome disassembly. Mol Cell https:\/\/doi.org\/10.1016\/j.molcel.2020.12.039","journal-title":"Mol Cell"},{"key":"BFEMBR202052164_CR61","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1242\/dev.101196","volume":"141","author":"HA Wallace","year":"2014","unstructured":"Wallace HA, Merkle JA, Yu MC, Berg TG, Lee E, Bosco G, Lee LA (2014) TRIP\/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase eta. Development 141: 1332\u20131341","journal-title":"Development"},{"key":"BFEMBR202052164_CR62","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41586-019-1002-0","volume":"567","author":"RA Wu","year":"2019","unstructured":"Wu RA, Semlow DR, Kamimae-Lanning AN, Kochenova OV, Chistol G, Hodskinson MR, Amunugama R, Sparks JL, Wang M, Deng L et al (2019) TRAIP is a master regulator of DNA interstrand crosslink repair. Nature 567: 267\u2013272","journal-title":"Nature"},{"key":"BFEMBR202052164_CR63","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00412-014-0500-y","volume":"124","author":"P Zegerman","year":"2015","unstructured":"Zegerman P (2015) Evolutionary conservation of the CDK targets in eukaryotic DNA replication initiation. Chromosoma 124: 309\u2013321","journal-title":"Chromosoma"}],"container-title":["The EMBO Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embr.202052164.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/embr.202052164","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/embr.202052164\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/embr.202052164","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embr.202052164.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:52:29Z","timestamp":1779112349000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/embr.202052164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,15]]},"references-count":63,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3,3]]}},"alternative-id":["BFEMBR202052164"],"URL":"https:\/\/doi.org\/10.15252\/embr.202052164","relation":{},"ISSN":["1469-221X","1469-3178"],"issn-type":[{"value":"1469-221X","type":"print"},{"value":"1469-3178","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,15]]},"assertion":[{"value":"24 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"EMBR202052164"}}