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Adv."],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:p>\n                    Fanconi anemia (FA) is characterized by bone marrow failure, congenital abnormalities, and cancer predisposition. Mutations in\n                    <jats:italic toggle=\"yes\">RAD51<\/jats:italic>\n                    paralogs have been identified in FA-like disorders and cancers. Although the role of RAD51 paralogs is well established in homologous recombination (HR)\u2013mediated DNA repair, little is known about their role during replication stress responses. Here, we report that the RAD51C-XRCC3 (CX3) complex of RAD51 paralogs participates in the FA pathway of R-loop tolerance mechanism. CX3 complex suppresses R-loops, transcription-replication collisions (TRCs), and associated genome instability under physiological and replication stress conditions. Mechanistically, the CX3 complex physically interacts with FANCM and facilitates its recruitment to the R-loop sites to promote its resolution. Notably, cells expressing the RAD51C R258H pathological mutant exhibit defective interaction with FANCM and display inefficient R-loop processing. The CX3 complex\u2013mediated R-loop resolution is independent of its fork maintenance function. Collectively, we demonstrate a previously unidentified role of the CX3 complex in preventing R-loop\u2013induced genome instability by regulating FANCM-mediated R-loop resolution.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea5932","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:58:58Z","timestamp":1771613938000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["RAD51C-XRCC3 complex regulates FANCM-mediated R-loop resolution to safeguard genome integrity"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1868-758X","authenticated-orcid":true,"given":"Satyaranjan","family":"Sahoo","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9339-1233","authenticated-orcid":true,"given":"Tarun","family":"Nagraj","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7976-4705","authenticated-orcid":true,"given":"Debanjali","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7864-5576","authenticated-orcid":true,"given":"Nupur","family":"Nagar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-7155","authenticated-orcid":true,"given":"Kumar","family":"Somyajit","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India."},{"name":"Functional Genomics and Metabolism Research Unit, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, Odense M 5230, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3801-7134","authenticated-orcid":true,"given":"Krishna Mohan","family":"Poluri","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-7095","authenticated-orcid":true,"given":"Ganesh","family":"Nagaraju","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0152-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.05.004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2007.02.020"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2025.102537"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.04.027"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-030222-115809"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2897"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-111212-133232"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.70025"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00474-x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.01.024"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.055"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0206-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01437-4"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2025.05.010"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-025-01669-y"},{"key":"e_1_3_2_19_2","first-page":"504","article-title":"RNA biogenesis and RNA metabolism factors as R-loop suppressors: A hidden role in genome integrity","volume":"38","author":"Luna R.","year":"2024","unstructured":"R. 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