{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:51:49Z","timestamp":1790805109107,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["249774"],"award-info":[{"award-number":["249774"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["270491"],"award-info":[{"award-number":["270491"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["291217"],"award-info":[{"award-number":["291217"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004590","name":"Helse Midt-Norge","doi-asserted-by":"publisher","award":["13477"],"award-info":[{"award-number":["13477"]}],"id":[{"id":"10.13039\/501100004590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008730","name":"Kreftforeningen","doi-asserted-by":"publisher","award":["182355"],"award-info":[{"award-number":["182355"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1 (MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)\/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.<\/jats:p>","DOI":"10.3390\/biom10010060","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T03:28:53Z","timestamp":1578022133000},"page":"60","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mediator of DNA Damage Checkpoint Protein 1 Facilitates V(D)J Recombination in Cells Lacking DNA Repair Factor XLF"],"prefix":"10.3390","volume":"10","author":[{"given":"Carole","family":"Beck","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Postboks 3250 Sluppen, 7006 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-6788","authenticated-orcid":false,"given":"Sergio","family":"Casta\u00f1eda-Zegarra","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Postboks 3250 Sluppen, 7006 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Huse","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Postboks 3250 Sluppen, 7006 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengtan","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Postboks 3250 Sluppen, 7006 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5088-3791","authenticated-orcid":false,"given":"Valentyn","family":"Oksenych","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Postboks 3250 Sluppen, 7006 Trondheim, Norway"},{"name":"Department of Biosciences and Nutrition (BioNuT), Karolinska Institutet, 14183 Huddinge, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.dnarep.2014.01.010","article-title":"Functional overlaps between XLF and the ATM-dependent DNA double strand break response","volume":"16","author":"Kumar","year":"2014","journal-title":"DNA Repair"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Oksenych, V., Zhovmer, A., Ziani, S., Mari, P.O., Eberova, J., Nardo, T., Stefanini, M., Giglia-Mari, G., Egly, J.M., and Coin, F. (2013). Histone methyltransferase DOT1L drives recovery of gene expression after a genotoxic attack. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003611"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.cell.2006.10.043","article-title":"Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair","volume":"127","author":"Botuyan","year":"2006","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nature03114","article-title":"Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks","volume":"432","author":"Huyen","year":"2004","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1038\/emboj.2010.27","article-title":"A cooperative activation loop among SWI\/SNF, gamma-H2AX and H3 acetylation for DNA double-strand break repair","volume":"29","author":"Lee","year":"2010","journal-title":"EMBO J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0092-8674(02)00671-2","article-title":"Hairpin opening and overhang processing by an Artemis\/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination","volume":"108","author":"Ma","year":"2002","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.cell.2005.12.031","article-title":"XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining","volume":"124","author":"Ahnesorg","year":"2006","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.cell.2005.12.030","article-title":"Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly","volume":"124","author":"Buck","year":"2006","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/cdd.2015.22","article-title":"XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair","volume":"22","author":"Craxton","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1126\/science.1261971","article-title":"DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair","volume":"347","author":"Ochi","year":"2015","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1038\/ncomms7233","article-title":"Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway","volume":"6","author":"Xing","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.molcel.2018.06.018","article-title":"MRI Is a DNA Damage Response Adaptor during Classical Non-homologous End Joining","volume":"71","author":"Hung","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Castaneda-Zegarra, S., Huse, C., R\u00f8sand, \u00d8., Sarno, A., Xing, M., Gago-Fuentes, R., Zhang, Q., Alirezaylavasani, A., Werner, J., and Ji, P. (2019). Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor Mri\/Cyren. Biomolecules, 9.","DOI":"10.20944\/preprints201911.0292.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cell.2013.01.007","article-title":"Mechanisms of programmed DNA lesions and genomic instability in the immune system","volume":"152","author":"Alt","year":"2013","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1074-7613(00)80386-6","article-title":"Growth retardation and leaky SCID phenotype of Ku70-deficient mice","volume":"7","author":"Gu","year":"1997","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/382551a0","article-title":"Requirement for Ku80 in growth and immunoglobulin V(D)J recombination","volume":"382","author":"Nussenzweig","year":"1996","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7378","DOI":"10.1073\/pnas.0601938103","article-title":"XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice","volume":"103","author":"Yan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1073\/pnas.1121470109","article-title":"Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1)","volume":"109","author":"Boboila","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/301527a0","article-title":"A severe combined immunodeficiency mutation in the mouse","volume":"301","author":"Bosma","year":"1983","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/S1097-2765(02)00755-4","article-title":"Leaky Scid phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice","volume":"10","author":"Rooney","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1073\/pnas.1019293108","article-title":"Ataxia telangiectasia-mutated protein and DNA-dependent protein kinase have complementary V(D)J recombination functions","volume":"108","author":"Zha","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.molcel.2015.02.024","article-title":"Differential phosphorylation of DNA-PKcs regulates the interplay between end-processing and end-ligation during nonhomologous end-joining","volume":"58","author":"Jiang","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S1074-7613(00)80619-6","article-title":"A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination","volume":"9","author":"Gao","year":"1998","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.molcel.2008.07.017","article-title":"Lymphocyte-specific compensation for XLF\/cernunnos end-joining functions in V(D)J recombination","volume":"31","author":"Li","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1128\/MCB.01057-12","article-title":"Cernunnos deficiency reduces thymocyte life span and alters the T cell repertoire in mice and humans","volume":"33","author":"Vera","year":"2013","journal-title":"Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1101\/gad.290510.116","article-title":"Synthetic lethality between PAXX and XLF in mammalian development","volume":"30","author":"Balmus","year":"2016","journal-title":"Genes Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/2211-5463.12381","article-title":"Normal development of mice lacking PAXX, the paralogue of XRCC4 and XLF","volume":"8","author":"Xing","year":"2018","journal-title":"FEBS Open Bio"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13816","DOI":"10.1038\/ncomms13816","article-title":"PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice","volume":"8","author":"Liu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/cdd.2017.184","article-title":"PAXX and Xlf interplay revealed by impaired CNS development and immunodeficiency of double KO mice","volume":"25","author":"Abramowski","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10619","DOI":"10.1073\/pnas.1611882113","article-title":"PAXX and XLF DNA repair factors are functionally redundant in joining DNA breaks in a G1-arrested progenitor B-cell line","volume":"113","author":"Kumar","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1080\/15384101.2016.1253640","article-title":"Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-homologous end joining in lymphocytes","volume":"16","author":"Hung","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1016\/j.celrep.2016.08.069","article-title":"Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination","volume":"16","author":"Lescale","year":"2016","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.dnarep.2018.12.002","article-title":"Synthetic lethality between DNA repair factors Xlf and Paxx is rescued by inactivation of Trp53","volume":"73","author":"Xing","year":"2019","journal-title":"DNA Repair"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1073\/pnas.1222573110","article-title":"Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V(D)J recombination and nonhomologous DNA end joining","volume":"110","author":"Oksenych","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.dnarep.2017.07.008","article-title":"Synthetic lethality between murine DNA repair factors XLF and DNA-PKcs is rescued by inactivation of Ku70","volume":"57","author":"Xing","year":"2017","journal-title":"DNA Repair"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10529","DOI":"10.1038\/ncomms10529","article-title":"RAG2 and XLF\/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair","volume":"7","author":"Lescale","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9302","DOI":"10.1073\/pnas.0803520105","article-title":"Complementary functions of ATM and H2AX in development and suppression of genomic instability","volume":"105","author":"Zha","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8173","DOI":"10.1073\/pnas.122228699","article-title":"Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX","volume":"99","author":"Bassing","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0092-8674(03)00566-X","article-title":"Histone H2AX: A dosage-dependent suppressor of oncogenic translocations and tumors","volume":"114","author":"Bassing","year":"2003","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.molcel.2005.11.025","article-title":"MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals","volume":"21","author":"Lou","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/ni1067","article-title":"53BP1 links DNA damage-response pathways to immunoglobulin heavy chain class-switch recombination","volume":"5","author":"Manis","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/nature09604","article-title":"ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks","volume":"469","author":"Zha","year":"2011","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1073\/pnas.1121458109","article-title":"Functional redundancy between repair factor XLF and damage response mediator 53BP1 in V(D)J recombination and DNA repair","volume":"109","author":"Oksenych","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1073\/pnas.1120160109","article-title":"Overlapping functions between XLF repair protein and 53BP1 DNA damage response factor in end joining and lymphocyte development","volume":"109","author":"Liu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1084\/jem.20110325","article-title":"Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis","volume":"209","author":"Du","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/414666a","article-title":"NEJ1 controls non-homologous end joining in Saccharomyces cerevisiae","volume":"414","author":"Valencia","year":"2001","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.1038\/s41467-019-12929-5","article-title":"MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance","volume":"10","author":"Salguero","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.molcel.2019.02.014","article-title":"MDC1 Interacts with TOPBP1 to Maintain Chromosomal Stability during Mitosis","volume":"74","author":"Leimbacher","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature04866","article-title":"ATM stabilizes DNA double-strand-break complexes during V(D)J recombination","volume":"442","author":"Bredemeyer","year":"2006","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jim.2017.08.007","article-title":"Generation and CRISPR\/Cas9 editing of transformed progenitor B cells as a pseudo-physiological system to study DNA repair gene function in V(D)J recombination","volume":"451","author":"Lescale","year":"2017","journal-title":"J. Immunol. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/2211-5463.12380","article-title":"Robust DNA repair in PAXX-deficient mammalian cells","volume":"8","author":"Dewan","year":"2018","journal-title":"FEBS Open Bio"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved vectors and genome-wide libraries for CRISPR screening","volume":"11","author":"Sanjana","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/0092-8674(91)90362-3","article-title":"bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship","volume":"67","author":"Strasser","year":"1991","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Xing, M., and Oksenych, V. (2019). Genetic interaction between DNA repair factors PAXX, XLF, XRCC4 and DNA-PKcs in human cells. FEBS Open Bio.","DOI":"10.1002\/2211-5463.12681"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nature09585","article-title":"H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes","volume":"469","author":"Helmink","year":"2011","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.dnarep.2014.04.004","article-title":"Reprint of \u201cFunctional overlaps between XLF and the ATM-dependent DNA double strand break response\u201d","volume":"17","author":"Kumar","year":"2014","journal-title":"DNA Repair"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1073\/pnas.1013295108","article-title":"Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation","volume":"108","author":"Gapud","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41556-018-0140-1","article-title":"Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells","volume":"20","author":"Dev","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/15384101.2019.1693118","article-title":"DNA damage responses in murine Pre-B cells with genetic deficiencies in damage response genes","volume":"19","author":"Innes","year":"2020","journal-title":"Cell Cycle"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature09755","article-title":"The RAG2 C terminus suppresses genomic instability and lymphomagenesis","volume":"471","author":"Deriano","year":"2011","journal-title":"Nature"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/1\/60\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:46:50Z","timestamp":1760190410000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/1\/60"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,30]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["biom10010060"],"URL":"https:\/\/doi.org\/10.3390\/biom10010060","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201912.0368.v1","asserted-by":"object"}]},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,30]]}}}