{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:27:14Z","timestamp":1793053634733,"version":"4.5.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tumor suppressor p53-binding protein 1 (53BP1) regulates DNA end joining in lymphocytes, diversifying immune antigen receptors. This involves nucleosome-bound 53BP1 at DNA double-stranded breaks (DSBs) recruiting Rap1-interacting factor 1 homolog (RIF1) and shieldin, a poorly understood DNA-binding complex. The 53BP1\u2013RIF1\u2013shieldin axis is pathological in\n                    <jats:italic>BRCA1<\/jats:italic>\n                    -mutated cancers, blocking homologous recombination (HR) and driving illegitimate nonhomologous end joining (NHEJ). However, how this axis regulates DNA end joining and HR suppression remains unresolved. We investigated shieldin and its interplay with the Ctc1\u2013Stn1\u2013Ten1 (CST) complex, which was recently implicated downstream of 53BP1. Immunophenotypically, mice lacking shieldin or CST are equivalent, with class-switch recombination coreliant on both complexes. Ataxia-telangiectasia mutated kinase-dependent DNA damage signaling underpins this cooperation, inducing physical interactions between these complexes that reveal shieldin as a DSB-responsive CST adaptor. Furthermore, DNA polymerase \u03b6 functions downstream of shieldin, establishing DNA fill-in synthesis as the physiological function of shieldin\u2013CST. Lastly, we demonstrate that 53BP1 suppresses HR and promotes NHEJ in\n                    <jats:italic>BRCA1<\/jats:italic>\n                    -deficient mice and cells independently of shieldin. These findings showcase the versatility of the 53BP1 pathway, achieved through the collaboration of chromatin-bound 53BP1 complexes and DNA end-processing effector proteins.\n                  <\/jats:p>","DOI":"10.1038\/s41594-024-01381-9","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T06:02:01Z","timestamp":1725343321000},"page":"86-97","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Shieldin and CST co-orchestrate DNA polymerase-dependent tailed-end joining reactions independently of 53BP1-governed repair pathway choice"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-900X","authenticated-orcid":false,"given":"Ashleigh","family":"King","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6400-8937","authenticated-orcid":false,"given":"Pia I.","family":"Reichl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1561-2782","authenticated-orcid":false,"given":"Jean S.","family":"Metson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella","family":"Munro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Sommerova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan R.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Biggs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Preece","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3623-600X","authenticated-orcid":false,"given":"Benjamin","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-4254","authenticated-orcid":false,"given":"J. Ross","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,3]]},"reference":[{"key":"1381_CR1","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1038\/nature08467","volume":"461","author":"SP Jackson","year":"2009","unstructured":"Jackson, S. P. & Bartek, J. The DNA-damage response in human biology and disease. Nature 461, 1071\u20131078 (2009).","journal-title":"Nature"},{"key":"1381_CR2","doi-asserted-by":"publisher","first-page":"102874","DOI":"10.1016\/j.dnarep.2020.102874","volume":"94","author":"XS Wang","year":"2020","unstructured":"Wang, X. S., Lee, B. J. & Zha, S. The recent advances in non-homologous end-joining through the lens of lymphocyte development. DNA Repair (Amst.) 94, 102874 (2020).","journal-title":"DNA Repair (Amst.)"},{"key":"1381_CR3","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/s41580-019-0152-0","volume":"20","author":"R Scully","year":"2019","unstructured":"Scully, R., Panday, A., Elango, R. & Willis, N. A. DNA double-strand break repair-pathway choice in somatic mammalian cells. Nat. Rev. Mol. Cell Biol. 20, 698\u2013714 (2019).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1381_CR4","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.tibs.2020.10.005","volume":"46","author":"T Saha","year":"2021","unstructured":"Saha, T., Sundaravinayagam, D. & Di Virgilio, M. Charting a DNA repair roadmap for immunoglobulin class switch recombination. Trends Biochem. Sci. 46, 184\u2013199 (2021).","journal-title":"Trends Biochem. Sci."},{"key":"1381_CR5","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/s41586-021-03716-8","volume":"596","author":"Q Hu","year":"2021","unstructured":"Hu, Q. et al. Mechanisms of BRCA1\u2013BARD1 nucleosome recognition and ubiquitylation. Nature 596, 438\u2013443 (2021).","journal-title":"Nature"},{"key":"1381_CR6","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature12318","volume":"499","author":"A Fradet-Turcotte","year":"2013","unstructured":"Fradet-Turcotte, A. et al. 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature 499, 50\u201354 (2013).","journal-title":"Nature"},{"key":"1381_CR7","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.molcel.2013.01.002","volume":"49","author":"JR Chapman","year":"2013","unstructured":"Chapman, J. R. et al. RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection. Mol. Cell 49, 858\u2013871 (2013).","journal-title":"Mol. Cell"},{"key":"1381_CR8","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1016\/j.molcel.2022.01.025","volume":"82","author":"D Setiaputra","year":"2022","unstructured":"Setiaputra, D. et al. RIF1 acts in DNA repair through phosphopeptide recognition of 53BP1. Mol. Cell 82, 1359\u20131371 e9 (2022).","journal-title":"Mol. Cell"},{"key":"1381_CR9","doi-asserted-by":"publisher","first-page":"e47560","DOI":"10.15252\/embr.201847560","volume":"20","author":"D Setiaputra","year":"2019","unstructured":"Setiaputra, D. & Durocher, D. Shieldin\u2014the protector of DNA ends. EMBO Rep. 20, e47560 (2019).","journal-title":"EMBO Rep."},{"key":"1381_CR10","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/nature07476","volume":"456","author":"S Difilippantonio","year":"2008","unstructured":"Difilippantonio, S. et al. 53BP1 facilitates long-range DNA end-joining during V(D)J recombination. Nature 456, 529\u2013533 (2008).","journal-title":"Nature"},{"key":"1381_CR11","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/s41586-018-0362-1","volume":"560","author":"H Ghezraoui","year":"2018","unstructured":"Ghezraoui, H. et al. 53BP1 cooperation with the REV7\u2013shieldin complex underpins DNA structure-specific NHEJ. Nature 560, 122\u2013127 (2018).","journal-title":"Nature"},{"key":"1381_CR12","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201949823","volume":"21","author":"AK Ling","year":"2020","unstructured":"Ling, A. K. et al. SHLD2 promotes class switch recombination by preventing inactivating deletions within the Igh locus. EMBO Rep. 21, e49823 (2020).","journal-title":"EMBO Rep."},{"key":"1381_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31287-3","volume":"13","author":"E Vincendeau","year":"2022","unstructured":"Vincendeau, E. et al. SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination. Nat. Commun. 13, 3707 (2022).","journal-title":"Nat. Commun."},{"key":"1381_CR14","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41586-021-03776-w","volume":"596","author":"JR Becker","year":"2021","unstructured":"Becker, J. R. et al. BARD1 reads H2A lysine 15 ubiquitination to direct homologous recombination. Nature 596, 433\u2013437 (2021).","journal-title":"Nature"},{"key":"1381_CR15","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/s41556-019-0282-9","volume":"21","author":"K Nakamura","year":"2019","unstructured":"Nakamura, K. et al. H4K20me0 recognition by BRCA1\u2013BARD1 directs homologous recombination to sister chromatids. Nat. Cell Biol. 21, 311\u2013318 (2019).","journal-title":"Nat. Cell Biol."},{"key":"1381_CR16","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2010.03.012","volume":"141","author":"SF Bunting","year":"2010","unstructured":"Bunting, S. F. et al. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141, 243\u2013254 (2010).","journal-title":"Cell"},{"key":"1381_CR17","doi-asserted-by":"publisher","first-page":"3529","DOI":"10.1242\/jcs.105353","volume":"125","author":"JR Chapman","year":"2012","unstructured":"Chapman, J. R., Sossick, A. J., Boulton, S. J. & Jackson, S. P. BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair. J. Cell Sci. 125, 3529\u20133534 (2012).","journal-title":"J. Cell Sci."},{"key":"1381_CR18","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1038\/nm.3369","volume":"19","author":"CJ Lord","year":"2013","unstructured":"Lord, C. J. & Ashworth, A. Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat. Med. 19, 1381\u20131388 (2013).","journal-title":"Nat. Med."},{"key":"1381_CR19","doi-asserted-by":"publisher","first-page":"2552","DOI":"10.1038\/s41418-020-0521-4","volume":"27","author":"J Chen","year":"2020","unstructured":"Chen, J. et al. 53BP1 loss rescues embryonic lethality but not genomic instability of BRCA1 total knockout mice. Cell Death Differ. 27, 2552\u20132567 (2020).","journal-title":"Cell Death Differ."},{"key":"1381_CR20","doi-asserted-by":"publisher","first-page":"3513","DOI":"10.1016\/j.celrep.2018.08.086","volume":"24","author":"J Nacson","year":"2018","unstructured":"Nacson, J. et al. BRCA1 mutation-specific responses to 53BP1 loss-induced homologous recombination and PARP inhibitor resistance. Cell Rep. 24, 3513\u20133527 (2018).","journal-title":"Cell Rep."},{"key":"1381_CR21","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1038\/s41556-018-0140-1","volume":"20","author":"H Dev","year":"2018","unstructured":"Dev, H. et al. Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells. Nat. Cell Biol. 20, 954\u2013965 (2018).","journal-title":"Nat. Cell Biol."},{"key":"1381_CR22","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41586-018-0340-7","volume":"560","author":"SM Noordermeer","year":"2018","unstructured":"Noordermeer, S. M. et al. The shieldin complex mediates 53BP1-dependent DNA repair. Nature 560, 117\u2013121 (2018).","journal-title":"Nature"},{"key":"1381_CR23","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nature14328","volume":"521","author":"G Xu","year":"2015","unstructured":"Xu, G. et al. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature 521, 541\u2013544 (2015).","journal-title":"Nature"},{"key":"1381_CR24","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1016\/j.celrep.2018.04.046","volume":"23","author":"M Barazas","year":"2018","unstructured":"Barazas, M. et al. The CST complex mediates end protection at double-strand breaks and promotes PARP inhibitor sensitivity in BRCA1-deficient cells. Cell Rep. 23, 2107\u20132118 (2018).","journal-title":"Cell Rep."},{"key":"1381_CR25","doi-asserted-by":"publisher","first-page":"e100158","DOI":"10.15252\/embj.2018100158","volume":"37","author":"S Findlay","year":"2018","unstructured":"Findlay, S. et al. SHLD2\/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice. EMBO J. 37, e100158 (2018).","journal-title":"EMBO J."},{"key":"1381_CR26","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1016\/j.cell.2018.03.050","volume":"173","author":"R Gupta","year":"2018","unstructured":"Gupta, R. et al. DNA repair network analysis reveals shieldin as a key regulator of NHEJ and PARP inhibitor sensitivity. Cell 173, 972\u2013988 (2018).","journal-title":"Cell"},{"key":"1381_CR27","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41586-018-0324-7","volume":"560","author":"Z Mirman","year":"2018","unstructured":"Mirman, Z. et al. 53BP1\u2013RIF1\u2013shieldin counteracts DSB resection through CST- and Pol \u03b1-dependent fill-in. Nature 560, 112\u2013116 (2018).","journal-title":"Nature"},{"key":"1381_CR28","doi-asserted-by":"publisher","first-page":"e99543","DOI":"10.15252\/embj.201899543","volume":"37","author":"J Tomida","year":"2018","unstructured":"Tomida, J. et al. FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells. EMBO J. 37, e99543 (2018).","journal-title":"EMBO J."},{"key":"1381_CR29","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41556-021-00812-9","volume":"24","author":"Z Mirman","year":"2022","unstructured":"Mirman, Z., Sasi, N. K., King, A., Chapman, J. R. & de Lange, T. 53BP1\u2013shieldin-dependent DSB processing in BRCA1-deficient cells requires CST\u2013Pol \u03b1\u2013primase fill-in synthesis. Nat. Cell Biol. 24, 51\u201361 (2022).","journal-title":"Nat. Cell Biol."},{"key":"1381_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25154-w","volume":"12","author":"J Schimmel","year":"2021","unstructured":"Schimmel, J., Munoz-Subirana, N., Kool, H., van Schendel, R. & Tijsterman, M. Small tandem DNA duplications result from CST-guided Pol \u03b1\u2013primase action at DNA break termini. Nat. Commun. 12, 4843 (2021).","journal-title":"Nat. Commun."},{"key":"1381_CR31","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1101\/gad.333237.119","volume":"34","author":"Z Mirman","year":"2020","unstructured":"Mirman, Z. & de Lange, T. 53BP1: a DSB escort. Genes Dev. 34, 7\u201323 (2020).","journal-title":"Genes Dev."},{"key":"1381_CR32","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/nprot.2015.010","volume":"10","author":"G Balmus","year":"2015","unstructured":"Balmus, G. et al. A high-throughput in vivo micronucleus assay for genome instability screening in mice. Nat. Protoc. 10, 205\u2013215 (2015).","journal-title":"Nat. Protoc."},{"key":"1381_CR33","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/ng.1084","volume":"44","author":"BH Anderson","year":"2012","unstructured":"Anderson, B. H. et al. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat. Genet. 44, 338\u2013342 (2012).","journal-title":"Nat. Genet."},{"key":"1381_CR34","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1038\/emboj.2012.96","volume":"31","author":"P Gu","year":"2012","unstructured":"Gu, P. et al. CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion. EMBO J. 31, 2309\u20132321 (2012).","journal-title":"EMBO J."},{"key":"1381_CR35","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature10163","volume":"474","author":"WC Skarnes","year":"2011","unstructured":"Skarnes, W. C. et al. A conditional knockout resource for the genome-wide study of mouse gene function. Nature 474, 337\u2013342 (2011).","journal-title":"Nature"},{"key":"1381_CR36","doi-asserted-by":"publisher","first-page":"D1038","DOI":"10.1093\/nar\/gkac972","volume":"51","author":"T Groza","year":"2023","unstructured":"Groza, T. et al. The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease. Nucleic Acids Res. 51, D1038\u2013D1045 (2023).","journal-title":"Nucleic Acids Res."},{"key":"1381_CR37","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.tcb.2008.08.005","volume":"18","author":"TA Kunkel","year":"2008","unstructured":"Kunkel, T. A. & Burgers, P. M. Dividing the workload at a eukaryotic replication fork. Trends Cell Biol. 18, 521\u2013527 (2008).","journal-title":"Trends Cell Biol."},{"key":"1381_CR38","doi-asserted-by":"publisher","first-page":"8348","DOI":"10.1093\/nar\/gkz705","volume":"47","author":"SK Martin","year":"2019","unstructured":"Martin, S. K. & Wood, R. D. DNA polymerase \u03b6 in DNA replication and repair. Nucleic Acids Res. 47, 8348\u20138361 (2019).","journal-title":"Nucleic Acids Res."},{"key":"1381_CR39","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1084\/jem.20080669","volume":"206","author":"D Schenten","year":"2009","unstructured":"Schenten, D. et al. Pol \u03b6 ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability. J. Exp. Med. 206, 477\u2013490 (2009).","journal-title":"J. Exp. Med."},{"key":"1381_CR40","doi-asserted-by":"publisher","first-page":"13789","DOI":"10.1073\/pnas.0605944103","volume":"103","author":"E Hobeika","year":"2006","unstructured":"Hobeika, E. et al. Testing gene function early in the B cell lineage in mb1-cre mice. Proc. Natl Acad. Sci. USA 103, 13789\u201313794 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1381_CR41","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/362847a0","volume":"362","author":"SW Lowe","year":"1993","unstructured":"Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A. & Jacks, T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362, 847\u2013849 (1993).","journal-title":"Nature"},{"key":"1381_CR42","doi-asserted-by":"publisher","first-page":"4473","DOI":"10.1093\/nar\/gks054","volume":"40","author":"SS Lange","year":"2012","unstructured":"Lange, S. S., Wittschieben, J. P. & Wood, R. D. DNA polymerase \u03b6 is required for proliferation of normal mammalian cells. Nucleic Acids Res. 40, 4473\u20134482 (2012).","journal-title":"Nucleic Acids Res."},{"key":"1381_CR43","doi-asserted-by":"publisher","first-page":"12111","DOI":"10.1073\/pnas.0702969104","volume":"104","author":"X Liu","year":"2007","unstructured":"Liu, X. et al. Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1-mutated basal-like breast cancer. Proc. Natl Acad. Sci. USA 104, 12111\u201312116 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1381_CR44","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/S0092-8674(00)81302-1","volume":"85","author":"R Hakem","year":"1996","unstructured":"Hakem, R. et al. The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. Cell 85, 1009\u20131023 (1996).","journal-title":"Cell"},{"key":"1381_CR45","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.15252\/embr.201642497","volume":"17","author":"M Li","year":"2016","unstructured":"Li, M. et al. 53BP1 ablation rescues genomic instability in mice expressing \u2018RING-less\u2019 BRCA1. EMBO Rep. 17, 1532\u20131541 (2016).","journal-title":"EMBO Rep."},{"key":"1381_CR46","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1158\/2159-8290.CD-12-0049","volume":"3","author":"JE Jaspers","year":"2013","unstructured":"Jaspers, J. E. et al. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer Discov. 3, 68\u201381 (2013).","journal-title":"Cancer Discov."},{"key":"1381_CR47","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1101\/gad.350479.123","volume":"37","author":"SW Cai","year":"2023","unstructured":"Cai, S. W. & de Lange, T. CST\u2013Pol \u03b1\/primase: the second telomere maintenance machine. Genes Dev. 37, 555\u2013569 (2023).","journal-title":"Genes Dev."},{"key":"1381_CR48","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1126\/science.1230624","volume":"339","author":"M Di Virgilio","year":"2013","unstructured":"Di Virgilio, M. et al. Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339, 711\u2013715 (2013).","journal-title":"Science"},{"key":"1381_CR49","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s00335-021-09894-0","volume":"33","author":"J Amos-Landgraf","year":"2022","unstructured":"Amos-Landgraf, J. et al. The Mutant Mouse Resource and Research Center (MMRRC): the NIH-supported national public repository and distribution archive of mutant mouse models in the USA. Mamm. Genome 33, 203\u2013212 (2022).","journal-title":"Mamm. Genome"},{"key":"1381_CR50","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/s41586-024-07137-1","volume":"627","author":"H Takai","year":"2024","unstructured":"Takai, H., Aria, V., Borges, P., Yeeles, J. T. P. & de Lange, T. CST\u2013polymerase \u03b1\u2013primase solves a second telomere end-replication problem. Nature 627, 664\u2013670 (2024).","journal-title":"Nature"},{"key":"1381_CR51","doi-asserted-by":"publisher","first-page":"3638","DOI":"10.1016\/j.cell.2024.05.002","volume":"187","author":"SW Cai","year":"2024","unstructured":"Cai, S. W., Takai, H., Walz, T. & de Lange, T. POT1 recruits and regulates CST-Pol \u03b1\/primase at human telomeres. Cell 187, 3638\u20133651 (2024).","journal-title":"Cell"},{"key":"1381_CR52","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1126\/science.aat2477","volume":"361","author":"JM Pryor","year":"2018","unstructured":"Pryor, J. M. et al. Ribonucleotide incorporation enables repair of chromosome breaks by nonhomologous end joining. Science 361, 1126\u20131129 (2018).","journal-title":"Science"},{"key":"1381_CR53","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nri1395","volume":"4","author":"J Chaudhuri","year":"2004","unstructured":"Chaudhuri, J. & Alt, F. W. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat. Rev. Immunol. 4, 541\u2013552 (2004).","journal-title":"Nat. Rev. Immunol."},{"key":"1381_CR54","doi-asserted-by":"publisher","first-page":"10323","DOI":"10.1093\/nar\/gkt813","volume":"41","author":"JD Lormand","year":"2013","unstructured":"Lormand, J. D. et al. DNA polymerase \u03b4 stalls on telomeric lagging strand templates independently from G-quadruplex formation. Nucleic Acids Res. 41, 10323\u201310333 (2013).","journal-title":"Nucleic Acids Res."},{"key":"1381_CR55","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/nmeth.4535","volume":"15","author":"AA Duarte","year":"2018","unstructured":"Duarte, A. A. et al. BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance. Nat. Methods 15, 134\u2013140 (2018).","journal-title":"Nat. Methods"},{"key":"1381_CR56","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.molcel.2020.04.006","volume":"78","author":"J Nacson","year":"2020","unstructured":"Nacson, J. et al. BRCA1 mutational complementation induces synthetic viability. Mol. Cell 78, 951\u2013959 (2020).","journal-title":"Mol. Cell"},{"key":"1381_CR57","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1023\/A:1008868325009","volume":"7","author":"Y Lallemand","year":"1998","unstructured":"Lallemand, Y., Luria, V., Haffner-Krausz, R. & Lonai, P. Maternally expressed PGK-Cre transgene as a tool for early and uniform activation of the Cre site-specific recombinase. Transgenic Res. 7, 105\u2013112 (1998).","journal-title":"Transgenic Res."},{"key":"1381_CR58","doi-asserted-by":"publisher","first-page":"D1171","DOI":"10.1093\/nar\/gku1193","volume":"43","author":"INFRAFRONTIER Consortium","year":"2015","unstructured":"INFRAFRONTIER ConsortiumINFRAFRONTIER\u2014providing mutant mouse resources as research tools for the international scientific community. Nucleic Acids Res. 43, D1171\u2013D1175 (2015).","journal-title":"Nucleic Acids Res."},{"key":"1381_CR59","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.1128\/MCB.23.7.2556-2563.2003","volume":"23","author":"IM Ward","year":"2003","unstructured":"Ward, I. M., Minn, K., van Deursen, J. & Chen, J. p53 binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol. Cell. Biol. 23, 2556\u20132563 (2003).","journal-title":"Mol. Cell. Biol."}],"container-title":["Nature Structural &amp; Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41594-024-01381-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-024-01381-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-024-01381-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T18:02:26Z","timestamp":1737396146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41594-024-01381-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,3]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["1381"],"URL":"https:\/\/doi.org\/10.1038\/s41594-024-01381-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.12.20.572534","asserted-by":"object"}]},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,3]]},"assertion":[{"value":"6 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}