FIRRM cooperates with FIGNL1 to promote RAD51 disassembly during DNA repair.

Autor:	Pinedo-Carpio E; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada.; Division of Experimental Medicine, McGill University, Montréal, QC H4A 3J1, Canada., Dessapt J; CHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Laval University Cancer Research Center, Québec, QC G1R 3S3, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1V 0A6, Canada., Beneyton A; CHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Laval University Cancer Research Center, Québec, QC G1R 3S3, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1V 0A6, Canada., Sacre L; Department of Biochemistry, McGill University, Montréal, QC H3G 0B1, Canada., Bérubé MA; CHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Laval University Cancer Research Center, Québec, QC G1R 3S3, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1V 0A6, Canada., Villot R; Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC H3C 3J7, Canada.; Maisonneuve-Rosemont Hospital Research Centre, Montréal, QC H1T 2M4 Canada., Lavoie EG; CHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Laval University Cancer Research Center, Québec, QC G1R 3S3, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1V 0A6, Canada., Coulombe Y; CHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Laval University Cancer Research Center, Québec, QC G1R 3S3, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1V 0A6, Canada., Blondeau A; CHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Laval University Cancer Research Center, Québec, QC G1R 3S3, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1V 0A6, Canada., Boulais J; Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada., Malina A; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada.; Maisonneuve-Rosemont Hospital Research Centre, Montréal, QC H1T 2M4 Canada., Luo VM; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada.; Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada., Lazaratos AM; Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC H3C 3J7, Canada.; Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada., Côté JF; Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada.; Département de Médecine, Université de Montréal, Montréal, QC H3C 3J7 Canada., Mallette FA; Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC H3C 3J7, Canada.; Maisonneuve-Rosemont Hospital Research Centre, Montréal, QC H1T 2M4 Canada.; Département de Médecine, Université de Montréal, Montréal, QC H3C 3J7 Canada., Guarné A; Department of Biochemistry, McGill University, Montréal, QC H3G 0B1, Canada., Masson JY; CHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Laval University Cancer Research Center, Québec, QC G1R 3S3, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1V 0A6, Canada., Fradet-Turcotte A; CHU de Québec Research Center-Université Laval (L'Hôtel-Dieu de Québec), Laval University Cancer Research Center, Québec, QC G1R 3S3, Canada.; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1V 0A6, Canada., Orthwein A; Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada.; Division of Experimental Medicine, McGill University, Montréal, QC H4A 3J1, Canada.; Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada.; Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada.; Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.; Gerald Bronfman Department of Oncology, McGill University, Montréal, QC H4A 3T2, Canada.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2023 Aug 09; Vol. 9 (32), pp. eadf4082. Date of Electronic Publication: 2023 Aug 09.
DOI:	10.1126/sciadv.adf4082
Abstrakt:	Interstrand DNA cross-links (ICLs) represent complex lesions that compromise genomic stability. Several pathways have been involved in ICL repair, but the extent of factors involved in the resolution of ICL-induced DNA double-strand breaks (DSBs) remains poorly defined. Using CRISPR-based genomics, we identified FIGNL1 interacting regulator of recombination and mitosis (FIRRM) as a sensitizer of the ICL-inducing agent mafosfamide. Mechanistically, we showed that FIRRM, like its interactor Fidgetin like 1 (FIGNL1), contributes to the resolution of RAD51 foci at ICL-induced DSBs. While the stability of FIGNL1 and FIRRM is interdependent, expression of a mutant of FIRRM (∆WCF), which stabilizes the protein in the absence of FIGNL1, allows the resolution of RAD51 foci and cell survival, suggesting that FIRRM has FIGNL1-independent function during DNA repair. In line with this model, FIRRM binds preferentially single-stranded DNA in vitro, raising the possibility that it directly contributes to RAD51 disassembly by interacting with DNA. Together, our findings establish FIRRM as a promoting factor of ICL repair.
Databáze:	MEDLINE
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