{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:17:12Z","timestamp":1789514232959,"version":"build-2803163510"},"reference-count":145,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Czech Ministry of Health","doi-asserted-by":"publisher","award":["NU22-03-00276"],"award-info":[{"award-number":["NU22-03-00276"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Czech Ministry of Health","doi-asserted-by":"publisher","award":["DRO-VFN-64165"],"award-info":[{"award-number":["DRO-VFN-64165"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Czech Ministry of Health","doi-asserted-by":"publisher","award":["SVV260516"],"award-info":[{"award-number":["SVV260516"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Czech Ministry of Health","doi-asserted-by":"publisher","award":["LX22NPO05102"],"award-info":[{"award-number":["LX22NPO05102"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Charles University","doi-asserted-by":"publisher","award":["NU22-03-00276"],"award-info":[{"award-number":["NU22-03-00276"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Charles University","doi-asserted-by":"publisher","award":["DRO-VFN-64165"],"award-info":[{"award-number":["DRO-VFN-64165"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Charles University","doi-asserted-by":"publisher","award":["SVV260516"],"award-info":[{"award-number":["SVV260516"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Charles University","doi-asserted-by":"publisher","award":["LX22NPO05102"],"award-info":[{"award-number":["LX22NPO05102"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2013Next Generation EU","award":["NU22-03-00276"],"award-info":[{"award-number":["NU22-03-00276"]}]},{"name":"European Union\u2013Next Generation EU","award":["DRO-VFN-64165"],"award-info":[{"award-number":["DRO-VFN-64165"]}]},{"name":"European Union\u2013Next Generation EU","award":["SVV260516"],"award-info":[{"award-number":["SVV260516"]}]},{"name":"European Union\u2013Next Generation EU","award":["LX22NPO05102"],"award-info":[{"award-number":["LX22NPO05102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The MRE11, RAD50, and NBN genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. Heterozygous germline alterations in the MRN complex genes have been associated with a poorly-specified predisposition to various cancer types. Somatic alterations in the MRN complex genes may represent valuable predictive and prognostic biomarkers in cancer patients. MRN complex genes have been targeted in several next-generation sequencing panels for cancer and neurological disorders, but interpretation of the identified alterations is challenging due to the complexity of MRN complex function in the DNA damage response. In this review, we outline the structural characteristics of the MRE11, RAD50 and NBN proteins, the assembly and functions of the MRN complex from the perspective of clinical interpretation of germline and somatic alterations in the MRE11, RAD50 and NBN genes.<\/jats:p>","DOI":"10.3390\/ijms24065612","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:53:44Z","timestamp":1678859624000},"page":"5612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Importance of Germline and Somatic Alterations in Human MRE11, RAD50, and NBN Genes Coding for MRN Complex"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-8320","authenticated-orcid":false,"given":"Barbora","family":"Otahalova","sequence":"first","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"},{"name":"Department of Biochemistry, Faculty of Natural Science, Charles University in Prague, 12800 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Volkova","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2413-1542","authenticated-orcid":false,"given":"Jana","family":"Soukupova","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4806-9854","authenticated-orcid":false,"given":"Petra","family":"Kleiblova","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"},{"name":"Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2816-6769","authenticated-orcid":false,"given":"Marketa","family":"Janatova","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-657X","authenticated-orcid":false,"given":"Michal","family":"Vocka","sequence":"additional","affiliation":[{"name":"Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0987-1238","authenticated-orcid":false,"given":"Libor","family":"Macurek","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Cell Biology, Institute of Molecular Genetics, Czech Academy of Sciences, 14220 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2050-9667","authenticated-orcid":false,"given":"Zdenek","family":"Kleibl","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"},{"name":"Institute of Pathological Physiology, First Faculty of Medicine and General University Hospital in Prague, 12853 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1631\/jzus.B2000289","article-title":"MRN complex is an essential effector of DNA damage repair","volume":"22","author":"Qiu","year":"2021","journal-title":"J. Zhejiang Univ. B"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.3390\/biom5031912","article-title":"Targeting the Checkpoint to Kill Cancer Cells","volume":"5","author":"Benada","year":"2015","journal-title":"Biomolecules"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fgene.2021.823943","article-title":"The (Lack of) DNA Double-Strand Break Repair Pathway Choice during V(D)J Recombination","volume":"12","author":"Libri","year":"2022","journal-title":"Front. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"831620","DOI":"10.3389\/fgene.2022.831620","article-title":"Meiotic Genes and DNA Double Strand Break Repair in Cancer","volume":"13","author":"Lingg","year":"2022","journal-title":"Front. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/sj.embor.embor925","article-title":"The MRN complex: Coordinating and mediating the response to broken chromosomes","volume":"4","author":"Bree","year":"2003","journal-title":"EMBO Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.dnarep.2016.05.011","article-title":"End-processing nucleases and phosphodiesterases: An elite supporting cast for the non-homologous end joining pathway of DNA double-strand break repair","volume":"43","author":"Menon","year":"2016","journal-title":"DNA Repair"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1016\/j.febslet.2010.07.029","article-title":"The MRN complex in double-strand break repair and telomere maintenance","volume":"584","author":"Lamarche","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.molcel.2018.06.033","article-title":"20 Years of Mre11 Biology: No End in Sight","volume":"71","author":"Paull","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-biochem-062917-012415","article-title":"The MRE11\u2013RAD50\u2013NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair","volume":"87","author":"Syed","year":"2018","journal-title":"Annu. Rev. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1139\/O07-069","article-title":"Mre11-Rad50-Nbs1 is a keystone complex connecting DNA repair machinery, double-strand break signaling, and the chromatin template","volume":"85","author":"Williams","year":"2007","journal-title":"Biochem. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R455","DOI":"10.1016\/j.cub.2008.03.040","article-title":"The MRN complex","volume":"18","author":"Rupnik","year":"2008","journal-title":"Curr. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1091\/mbc.e13-01-0025","article-title":"The Mre11-Rad50-Nbs1 (MRN) complex has a specific role in the activation of Chk1 in response to stalled replication forks","volume":"24","author":"Lee","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s12943-019-1100-5","article-title":"MRE11-RAD50-NBS1 complex alterations and DNA damage response: Implications for cancer treatment","volume":"18","author":"Bian","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.molcel.2022.12.003","article-title":"Cryo-EM structure of the Mre11-Rad50-Nbs1 complex reveals the molecular mechanism of scaffolding functions","volume":"83","author":"Rotheneder","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nsmb.2323","article-title":"Structure of Mre11\u2013Nbs1 complex yields insights into ataxia-telangiectasia\u2013like disease mutations and DNA damage signaling","volume":"19","author":"Schiller","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"a017962","DOI":"10.1101\/cshperspect.a017962","article-title":"Structural Studies of DNA End Detection and Resection in Homologous Recombination","volume":"6","author":"Schiller","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cell.2009.07.033","article-title":"Nbs1 Flexibly Tethers Ctp1 and Mre11-Rad50 to Coordinate DNA Double-Strand Break Processing and Repair","volume":"139","author":"Williams","year":"2009","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1101\/gad.2037811","article-title":"Crystal structure of the Mre11-Rad50-ATP\u03b3S complex: Understanding the interplay between Mre11 and Rad50","volume":"25","author":"Lim","year":"2011","journal-title":"Genes Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1242\/bio.20121834","article-title":"MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA","volume":"1","author":"Lee","year":"2012","journal-title":"Biol. Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.pbiomolbio.2014.12.004","article-title":"Envisioning the dynamics and flexibility of Mre11-Rad50-Nbs1 complex to decipher its roles in DNA replication and repair","volume":"117","author":"Williams","year":"2015","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0092-8674(01)00335-X","article-title":"Structural Biochemistry and Interaction Architecture of the DNA Double-Strand Break Repair Mre11 Nuclease and Rad50-ATPase","volume":"105","author":"Hopfner","year":"2001","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"44945","DOI":"10.1074\/jbc.M111.299347","article-title":"DNA repair factor MRE11\/RAD50 cleaves 3\u2032-phosphotyrosyl bonds and resects DNA to repair damage caused by topoisomerase 1 poisons","volume":"286","author":"Sacho","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.str.2011.09.010","article-title":"Crystal Structure of Human Mre11: Understanding Tumorigenic Mutations","volume":"19","author":"Park","year":"2011","journal-title":"Structure"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.cell.2008.08.017","article-title":"Mre11 Dimers Coordinate DNA End Bridging and Nuclease Processing in Double-Strand-Break Repair","volume":"135","author":"Williams","year":"2008","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lu, R., Zhang, H., Jiang, Y.-N., Wang, Z.-Q., Sun, L., and Zhou, Z.-W. (2021). Post-Translational Modification of MRE11: Its Implication in DDR and Diseases. Genes, 12.","DOI":"10.3390\/genes12081158"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1128\/MCB.02025-07","article-title":"A Glycine-Arginine Domain in Control of the Human MRE11 DNA Repair Protein","volume":"28","author":"Coulombe","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.15698\/mic2016.08.517","article-title":"Functions and regulation of the MRX complex at DNA double-strand breaks","volume":"3","author":"Gobbini","year":"2016","journal-title":"Microb. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1042\/BST20170168","article-title":"Turning the Mre11\/Rad50 DNA repair complex on its head: Lessons from SMC protein hinges, dynamic coiled-coil movements and DNA loop-extrusion?","volume":"48","author":"Zabolotnaya","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.15252\/embj.201488889","article-title":"Structure of the Rad50 DNA double-strand break repair protein in complex with DNA","volume":"33","author":"Rojowska","year":"2014","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.jmb.2003.11.026","article-title":"The Rad50 Signature Motif: Essential to ATP Binding and Biological Function","volume":"335","author":"Moncalian","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nature00922","article-title":"The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair","volume":"418","author":"Hopfner","year":"2002","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e9197","DOI":"10.7717\/peerj.9197","article-title":"In silico analysis on the functional and structural impact of Rad50 mutations involved in DNA strand break repair","volume":"8","author":"Remali","year":"2020","journal-title":"PeerJ"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/nature03927","article-title":"Mesoscale conformational changes in the DNA-repair complex Rad50\/Mre11\/Nbs1 upon binding DNA","volume":"437","author":"Dekker","year":"2005","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nsmb.3369","article-title":"Eukaryotic Rad50 functions as a rod-shaped dimer","volume":"24","author":"Park","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"759","DOI":"10.15252\/embj.201592934","article-title":"Structural mechanism of ATP-dependent DNA binding and DNA end bridging by eukaryotic Rad50","volume":"35","author":"Seifert","year":"2016","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.molcel.2019.07.035","article-title":"Mechanism of DNA End Sensing and Processing by the Mre11-Rad50 Complex","volume":"76","author":"Saathoff","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1146\/annurev-genet-071719-020312","article-title":"DNA End Resection: Mechanism and Control","volume":"55","author":"Cejka","year":"2021","journal-title":"Annu. Rev. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0092-8674(00)81174-5","article-title":"Nibrin, a Novel DNA Double-Strand Break Repair Protein, Is Mutated in Nijmegen Breakage Syndrome","volume":"93","author":"Varon","year":"1998","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Cilli, D., Mirasole, C., Pennisi, R., Pallotta, V., D\u2032Alessandro, A., Antoccia, A., Zolla, L., Ascenzi, P., and di Masi, A. (2014). Identification of the Interactors of Human Nibrin (NBN) and of Its 26 kDa and 70 kDa Fragments Arising from the NBN 657del5 Founder Mutation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114651"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/embor.2008.103","article-title":"Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage","volume":"9","author":"Chapman","year":"2008","journal-title":"EMBO Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/nature01446","article-title":"MDC1 is a mediator of the mammalian DNA damage checkpoint","volume":"421","author":"Stewart","year":"2003","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1269\/jrr.08065","article-title":"Dancing on damaged chromatin: Functions of ATM and the RAD50\/MRE11\/NBS1 complex in cellular responses to DNA damage","volume":"49","author":"Iijima","year":"2008","journal-title":"J. Radiat. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1038\/onc.2017.99","article-title":"MRE11 stability is regulated by CK2-dependent interaction with R2TP complex","volume":"36","author":"Burdova","year":"2017","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0092-8674(00)81175-7","article-title":"The hMre11\/hRad50 protein complex and Nijmegen breakage syndrome: Linkage of double-strand break repair to the cellular DNA damage response","volume":"93","author":"Carney","year":"1998","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.celrep.2016.12.035","article-title":"The Mre11-Nbs1 Interface Is Essential for Viability and Tumor Suppression","volume":"18","author":"Kim","year":"2017","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.molcel.2016.10.017","article-title":"Phosphorylated CtIP Functions as a Co-factor of the MRE11-RAD50-NBS1 Endonuclease in DNA End Resection","volume":"64","author":"Anand","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s42764-022-00065-2","article-title":"MRE11-RAD50-NBS1-CtIP: One key nuclease ensemble functions in the maintenance of genome stability","volume":"3","author":"Zhang","year":"2022","journal-title":"Genome Instab. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.molcel.2022.12.016","article-title":"The ends in sight: Mre11-Rad50-Nbs1 complex structures come into focus","volume":"83","author":"Wojtaszek","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.cellsig.2011.12.023","article-title":"The BRCA1 alternative splicing variant \u039414-15 with an in-frame deletion of part of the regulatory serine-containing domain (SCD) impairs the DNA repair capacity in MCF-7 cells","volume":"24","author":"Sevcik","year":"2012","journal-title":"Cell. Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10549-006-9406-6","article-title":"The role of ATM in breast cancer development","volume":"104","author":"Prokopcova","year":"2006","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ueno, S., Sudo, T., and Hirasawa, A. (2022). ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010523"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(00)81547-0","article-title":"The DNA Double-Strand Break Repair Gene hMRE11 Is Mutated in Individuals with an Ataxia-Telangiectasia-like Disorder","volume":"99","author":"Stewart","year":"1999","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.molcel.2017.08.002","article-title":"Single-Molecule Imaging Reveals How Mre11-Rad50-Nbs1 Initiates DNA Break Repair","volume":"67","author":"Myler","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eaay0922","DOI":"10.1126\/sciadv.aay0922","article-title":"DNA-dependent protein kinase promotes DNA end processing by MRN and CtIP","volume":"6","author":"Deshpande","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.molcel.2016.10.011","article-title":"Mre11 Is Essential for the Removal of Lethal Topoisomerase 2 Covalent Cleavage Complexes","volume":"64","author":"Hoa","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nsmb.2212","article-title":"Mre11 regulates CtIP-dependent double-strand break repair by interaction with CDK2","volume":"19","author":"Buis","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/S1097-2765(00)80097-0","article-title":"The 3\u2032 to 5\u2032 Exonuclease Activity of Mre11 Facilitates Repair of DNA Double-Strand Breaks","volume":"1","author":"Paull","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"503438","DOI":"10.1016\/j.mrgentox.2021.503438","article-title":"Crosstalk between different DNA repair pathways for DNA double strand break repairs","volume":"873","author":"Oh","year":"2021","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1158\/1078-0432.CCR-21-1509","article-title":"MRN Complex and Cancer Risk: Old Bottles, New Wine","volume":"27","author":"Elkholi","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e31723","DOI":"10.7554\/eLife.31723","article-title":"p53 orchestrates DNA replication restart homeostasis by suppressing mutagenic RAD52 and POL\u03b8 pathways","volume":"7","author":"Roy","year":"2018","journal-title":"Elife"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cell.2011.03.041","article-title":"Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11","volume":"145","author":"Schlacher","year":"2011","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1038\/s12276-020-00519-1","article-title":"DNA end resection and its role in DNA replication and DSB repair choice in mammalian cells","volume":"52","author":"Zhao","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Borsos, B.N., Majoros, H., and Pankotai, T. (2020). Ubiquitylation-Mediated Fine-Tuning of DNA Double-Strand Break Repair. Cancers, 12.","DOI":"10.3390\/cancers12061617"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"102869","DOI":"10.1016\/j.dnarep.2020.102869","article-title":"The MRE11 complex: A versatile toolkit for the repair of broken DNA","volume":"91\u201392","author":"Reginato","year":"2020","journal-title":"DNA Repair"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41572-019-0113-0","article-title":"Chromosome instability syndromes","volume":"5","author":"Taylor","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/86920","article-title":"An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele","volume":"27","author":"Maser","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/hmg\/ddi482","article-title":"Mild Nijmegen breakage syndrome phenotype due to alternative splicing","volume":"15","author":"Varon","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1750-1172-7-13","article-title":"Nijmegen breakage syndrome (NBS)","volume":"7","author":"Chrzanowska","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Seemanova, E., Varon, R., Vejvalka, J., Jarolim, P., Seeman, P., Chrzanowska, K.H., Digweed, M., Resnick, I., Kremensky, I., and Saar, K. (2016). The Slavic NBN Founder Mutation: A Role for Reproductive Fitness?. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167984"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/mt.2015.144","article-title":"Directed Alternative Splicing in Nijmegen Breakage Syndrome: Proof of Principle Concerning Its Therapeutical Application","volume":"24","author":"Salewsky","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_71","first-page":"7263","article-title":"Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis","volume":"63","author":"Frappart","year":"2003","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Desjardins, S., Beauparlant, J.C., Labrie, Y., Ouellette, G., INHERIT BRCAs, and Francine Durocher (2009). Variations in the NBN\/NBS1 gene and the risk of breast cancer in non-BRCA1\/2 French Canadian families with high risk of breast cancer. BMC Cancer, 9.","DOI":"10.1186\/1471-2407-9-181"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/sj.ejhg.5200554","article-title":"Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations","volume":"8","author":"Varon","year":"2000","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1158\/1078-0432.CCR-20-2574","article-title":"Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome","volume":"27","author":"Pastorczak","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_75","first-page":"186","article-title":"Non-Hodgkin lymphoma (NHL) in children with Nijmegen Breakage syndrome (NBS)","volume":"52","author":"Perek","year":"2008","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.ijrobp.2009.02.057","article-title":"Clinical Radiation Sensitivity with DNA Repair Disorders: An Overview","volume":"74","author":"Pollard","year":"2009","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_77","first-page":"85","article-title":"Nijmegen breakage syndrome: Case report and review of literature","volume":"35","author":"Hasbaoui","year":"2020","journal-title":"Pan. Afr. Med. J."},{"key":"ref_78","first-page":"ECR27","article-title":"T-cell lymphoblastic leukemia\/lymphoma in Nijmegen breakage syndrome","volume":"89","author":"Pasic","year":"2004","journal-title":"Haematologica"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Rahman, S., Canny, M.D., Buschmann, T.A., and Latham, M.P. (2020). A Survey of Reported Disease-Related Mutations in the MRE11-RAD50-NBS1 Complex. Cells, 9.","DOI":"10.3390\/cells9071678"},{"key":"ref_80","first-page":"1875","article-title":"Cancer Risk of Heterozygotes With the NBN Founder Mutation","volume":"99","author":"Jarolim","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1002\/humu.23773","article-title":"Three new cases of ataxia-telangiectasia-like disorder: No impairment of the ATM pathway, but S-phase checkpoint defect","volume":"40","author":"Bellanger","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1002\/ajmg.a.61570","article-title":"Human RAD50 deficiency: Confirmation of a distinctive phenotype","volume":"182","author":"Ragamin","year":"2020","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1016\/j.neuroscience.2006.12.010","article-title":"A subgroup of spinocerebellar ataxias defective in DNA damage responses","volume":"145","author":"Gueven","year":"2007","journal-title":"Neuroscience"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"283","DOI":"10.4103\/jpn.JPN_152_19","article-title":"A rare case of ataxia-telangiectasia-like disorder with MRE11 mutation","volume":"15","author":"Mahale","year":"2020","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_85","unstructured":"Alsbeih, G. (2011). Human Genetic Diseases, IntechOpen."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1101\/gad.1746609","article-title":"Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS","volume":"23","author":"Shull","year":"2009","journal-title":"Genes Dev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/mdc3.13110","article-title":"Beyond Typical Ataxia Telangiectasia: How to Identify the Ataxia Telangiectasia-Like Disorders","volume":"8","author":"Raslan","year":"2020","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.dnarep.2010.12.002","article-title":"Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly","volume":"10","author":"Matsumoto","year":"2011","journal-title":"DNA Repair"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jpeds.2009.02.037","article-title":"Two Brothers with Ataxia-Telangiectasia-like Disorder with Lung Adenocarcinoma","volume":"155","author":"Uchisaka","year":"2009","journal-title":"J. Pediatr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ajhg.2009.04.010","article-title":"Human RAD50 Deficiency in a Nijmegen Breakage Syndrome-like Disorder","volume":"84","author":"Waltes","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1056\/NEJMoa2005936","article-title":"A Population-Based Study of Genes Previously Implicated in Breast Cancer","volume":"384","author":"Hu","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1056\/NEJMoa1913948","article-title":"Breast Cancer Risk Genes-Association Analysis in More than 113,000 Women","volume":"384","author":"Dorling","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/pros.24252","article-title":"Association of germline rare pathogenic mutations in guideline-recommended genes with prostate cancer progression: A meta-analysis","volume":"82","author":"Shi","year":"2021","journal-title":"Prostate"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/ijc.20239","article-title":"Increased cancer risk of heterozygotes withNBS1 germline mutations in poland","volume":"111","author":"Steffen","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Horackova, K.F., Zemankova, S., Nehasil, P., Cerna, P., Neroldova, M., Otahalova, M., Kral, B., Hovhannisyan, J., Stranecky, M., and Zima, V. (2022). Low Frequency of Cancer-Predisposition Gene Mutations in Liver Transplant Candidates with Hepatocellular Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15010201"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00401-009-0608-y","article-title":"Heterozygous germ-line mutations in the NBN gene predispose to medulloblastoma in pediatric patients","volume":"119","author":"Ciara","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/sj.ejhg.5200972","article-title":"Multiplex single-tube screening for mutations in the Nijmegen Breakage Syndrome (NBS1) gene in Hodgkin\u2032s and non-Hodgkin\u2032s lymphoma patients of Slavic origin","volume":"11","author":"Soucek","year":"2003","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1002\/humu.24057","article-title":"Candidate genes for hereditary colorectal cancer: Mutational screening and systematic review","volume":"41","author":"Belhadj","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s10350-005-0293-4","article-title":"Accumulation Profile of Frameshift Mutations during Development and Progression of Colorectal Cancer from Patients with Hereditary Nonpolyposis Colorectal Cancer","volume":"49","author":"Yamaguchi","year":"2006","journal-title":"Dis. Colon Rectum"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1158\/0008-5472.CAN-07-6272","article-title":"Mutational Analysis of Thirty-two Double-Strand DNA Break Repair Genes in Breast and Pancreatic Cancers","volume":"68","author":"Wang","year":"2008","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1093\/carcin\/bgi360","article-title":"RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability","volume":"27","author":"Heikkinen","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_102","first-page":"155","article-title":"Gene Panel Testing in Hereditary Breast Cancer","volume":"23","author":"Rostami","year":"2020","journal-title":"Arch. Iran. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"R58","DOI":"10.1186\/bcr3669","article-title":"Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: Results from a Breast Cancer Family Registry case-control mutation-screening study","volume":"16","author":"Damiola","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1158\/1055-9965.EPI-08-0971","article-title":"Rad50 c.687delT Does Not Contribute Significantly to Familial Breast Cancer in a French Population","volume":"18","author":"Uhrhammer","year":"2009","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Trubicka, J., \u017bemojtel, T., Hecht, J., Falana, K., Abramczuk, D.P., P\u0142oski, R., Perek-Polnik, M., Drogosiewicz, M., Grajkowska, W., and Ciara, E. (2017). The germline variants in DNA repair genes in pediatric medulloblastoma: A challenge for current therapeutic strategies. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3211-y"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/ijc.11231","article-title":"Germline 657del5 mutation in the NBS1 gene in breast cancer patients","volume":"106","author":"Mierzejewski","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_107","first-page":"3015","article-title":"Germline NBS1 mutations in families with aggregation of Breast and\/or ovarian cancer from north-east Poland","volume":"27","author":"Kanka","year":"2007","journal-title":"Anticancer. Res."},{"key":"ref_108","first-page":"343","article-title":"I171V germline mutation in the NBS1 gene significantly increases risk of breast cancer","volume":"110","author":"Mosor","year":"2007","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1001\/jamaoncol.2017.0424","article-title":"Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer","volume":"3","author":"Couch","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/cam4.1376","article-title":"Gene panel testing of 5589 BRCA1\/2-negative index patients with breast cancer in a routine diagnostic setting: Results of the German Consortium for Hereditary Breast and Ovarian Cancer","volume":"7","author":"Hauke","year":"2018","journal-title":"Cancer Med."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Rogo\u017ca-Janiszewska, E., Mali\u0144ska, K., Cybulski, C., Jakubowska, A., Gronwald, J., Huzarski, T., Lener, M., G\u00f3rski, B., Klu\u017aniak, W., and Rudnicka, H. (2020). Prevalence of Recurrent Mutations Predisposing to Breast Cancer in Early-Onset Breast Cancer Patients from Poland. Cancers, 12.","DOI":"10.3390\/cancers12082321"},{"key":"ref_112","first-page":"253","article-title":"Association between 15 known or potential breast cancer susceptibility genes and breast cancer risks in Chinese women","volume":"19","author":"Fu","year":"2021","journal-title":"Cancer Biol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.16.00066","article-title":"Breast and Ovarian Cancer Penetrance Estimates Derived from Germline Multiple-Gene Sequencing Results in Women","volume":"1","author":"Kurian","year":"2017","journal-title":"JCO Precis. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s10549-012-2049-x","article-title":"Germline mutations 657del5 and 643C>T (R215W) in NBN are not likely to be associated with increased risk of breast cancer in Czech women","volume":"133","author":"Mateju","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.mrfmmm.2009.04.004","article-title":"NBN 657del5 heterozygous mutations and colorectal cancer risk in the Czech Republic","volume":"666","author":"Pardini","year":"2009","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/ajmg.a.20188","article-title":"657del5 mutation in the gene for Nijmegen breakage syndrome (NBS1) in a cohort of Russian children with lymphoid tissue malignancies and controls","volume":"120A","author":"Resnick","year":"2003","journal-title":"Am. J. Med. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Stolarova, L., Jelinkova, S., Storchova, R., Machackova, E., Zemankova, P., Vocka, M., Kodet, O., Kral, J., Cerna, M., and Volkova, Z. (2020). Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100404"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"djv214","DOI":"10.1093\/jnci\/djv214","article-title":"Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women with Ovarian Cancer","volume":"107","author":"Ramus","year":"2015","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Lhotova, K., Stolarova, L., Zemankova, P., Vocka, M., Janatova, M., Borecka, M., Cerna, M., Jelinkova, S., Kral, J., and Volkova, Z. (2020). Multigene Panel Germline Testing of 1333 Czech Patients with Ovarian Cancer. Cancers, 12.","DOI":"10.3390\/cancers12040956"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/ijc.30116","article-title":"Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer?","volume":"139","author":"Lener","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.gene.2016.04.056","article-title":"The c.657del5 variant in the NBN gene predisposes to pancreatic cancer","volume":"587","author":"Borecka","year":"2016","journal-title":"Gene"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1158\/0008-5472.CAN-03-2502","article-title":"NBS1 Is a Prostate Cancer Susceptibility Gene","volume":"64","author":"Cybulski","year":"2004","journal-title":"Cancer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1158\/1055-9965.EPI-05-0910","article-title":"Role of the Nijmegen Breakage Syndrome 1 Gene in Familial and Sporadic Prostate Cancer","volume":"15","author":"Hebbring","year":"2006","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/bjc.2012.486","article-title":"An inherited NBN mutation is associated with poor prognosis prostate cancer","volume":"108","author":"Cybulski","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1002\/ijc.33272","article-title":"Mutations in ATM, NBN and BRCA2 predispose to aggressive prostate cancer in Poland","volume":"147","author":"Huzarski","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2018.78.5204","article-title":"Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma","volume":"36","author":"Panou","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.molonc.2008.09.007","article-title":"Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene","volume":"2","author":"Bartkova","year":"2008","journal-title":"Mol. Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1158\/1055-9965.EPI-07-0116","article-title":"Breast cancer risk is associated with the genes encoding the DNA double-strand break repair Mre11\/Rad50\/Nbs1 complex","volume":"16","author":"Hsu","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/ejhg.2014.16","article-title":"Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes","volume":"22","author":"Castera","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1038\/s41598-021-81106-w","article-title":"Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer","volume":"11","author":"Elkholi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_131","first-page":"407","article-title":"A clinical guide to hereditary cancer panel testing: Evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients","volume":"22","author":"LaDuca","year":"2019","journal-title":"Anesth. Analg."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41431-021-01013-6","article-title":"Multilocus Inherited Neoplasia Allele Syndrome (MINAS): An update","volume":"30","author":"McGuigan","year":"2022","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1158\/1078-0432.CCR-13-2287","article-title":"Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas","volume":"20","author":"Pennington","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nrc3748","article-title":"New PARP targets for cancer therapy","volume":"14","author":"Vyas","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S1470-2045(11)70214-5","article-title":"Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: A phase 2, multicentre, open-label, non-randomised study","volume":"12","author":"Gelmon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/S1470-2045(21)00376-4","article-title":"Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): An open-label, phase 2 trial","volume":"22","author":"Mehra","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Fumet, J.-D., Limagne, E., Thibaudin, M., Truntzer, C., Bertaut, A., Rederstorff, E., and Ghiringhelli, F. (2020). Precision medicine phase II study evaluating the efficacy of a double immunotherapy by durvalumab and tremelimumab combined with olaparib in patients with solid cancers and carriers of homologous recombination repair genes mutation in response or stable after olaparib treatment. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07253-x"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"McPherson, M.T., Holub, A.S., Husbands, A.Y., and Petreaca, R.C. (2020). Mutation Spectra of the MRN (MRE11, RAD50, NBS1\/NBN) Break Sensor in Cancer Cells. Cancers, 12.","DOI":"10.3390\/cancers12123794"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1158\/2159-8290.CD-14-0380","article-title":"Synthetic Lethality in ATM-Deficient RAD50-Mutant Tumors Underlies Outlier Response to Cancer Therapy","volume":"4","author":"Iyer","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1093\/nar\/gkz1228","article-title":"Adjacent mutations in the archaeal Rad50 ABC ATPase D-loop disrupt allosteric regulation of ATP hydrolysis through different mechanisms","volume":"48","author":"Boswell","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1016958","DOI":"10.3389\/fonc.2022.1016958","article-title":"Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy","volume":"12","author":"Seborova","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"23312","DOI":"10.18632\/oncotarget.8196","article-title":"Genomic landscape of DNA repair genes in cancer","volume":"7","author":"Chae","year":"2016","journal-title":"Oncotarget"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.7150\/thno.39341","article-title":"Copy Number Amplification of DNA Damage Repair Pathways Potentiates Therapeutic Resistance in Cancer","volume":"10","author":"Wu","year":"2020","journal-title":"Theranostics"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"S116","DOI":"10.1016\/S0167-8140(15)30405-9","article-title":"PD-0300: NBN gain is predictive for adverse outcome following image-guided radiotherapy for localized prostate cancer","volume":"111","author":"Berlin","year":"2014","journal-title":"Radiother. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/s41586-020-2430-6","article-title":"Monogenic and polygenic inheritance become instruments for clonal selection","volume":"584","author":"Loh","year":"2020","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5612\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:55:36Z","timestamp":1760122536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":145,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065612"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065612","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]}}}