Sir3 Heterochromatin Protein Promotes NHEJ by Direct Inhibition of Sae2
Sir3 Heterochromatin Protein Promotes NHEJ by Direct Inhibition of Sae2
Abstract Heterochromatin is a conserved feature of eukaryotic chromosomes, with central roles in gene expression regulation and maintenance of genome stability. How DNA repair occurs in heterochromatin remains poorly described. In Saccharomyces cerevisiae, the Silent Information Regulator (SIR) complex assembles heterochromatin-like chromatin at subtelomeres. SIR-mediated repressive chromatin limits double strand break (DSB) resection protecting damaged chromosome ends during HR. As resection initiation marks the cross-road between repair by non-homologous end joining (NHEJ) or HR, we asked whether SIR-mediated heterochromatin regulates NHEJ. We show that SIRs promotes NHEJ through two pathways, one depending on repressive chromatin assembly, and the other relying on Sir3 in a manner that is independent of its heterochromatin-promoting function. Sir3 is a potent inhibitor of Sae2-dependent MRX functions. Sir3 physically interacts with Sae2 and this interaction impairs Sae2 interaction with MRX. As a consequence, Sir3 limits Mre11-mediated resection, delays MRX removal from DSB ends and promotes NHEJ.
Brocas Cl¨|mentine、Veaute Xavier、Dubrana Karine、Gu¨|rois Rapha?l、Busso Didier、Costa Rafa?l、Bordelet H¨|l¨¨ne、Batt¨| Amandine、Depagne Jordane、Marcand St¨|phane
Universit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et RadiationsCIGEx platform. Universit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et RadiationsUniversit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et RadiationsInstitute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Universit¨| Paris-Sud, Universit¨| Paris-SaclayCIGEx platform. Universit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et RadiationsUniversit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et RadiationsUniversit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et Radiations||R¨|gulation spatiale des g¨|nomes, Institut PasteurUniversit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et Radiations||Center for Integrative Genomics, Batiment G¨|nopode, University of LausanneCIGEx platform. Universit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et RadiationsUniversit¨| de Paris and Universit¨| Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilit¨| G¨|n¨|tique Cellules Souches et Radiations
分子生物学遗传学
Brocas Cl¨|mentine,Veaute Xavier,Dubrana Karine,Gu¨|rois Rapha?l,Busso Didier,Costa Rafa?l,Bordelet H¨|l¨¨ne,Batt¨| Amandine,Depagne Jordane,Marcand St¨|phane.Sir3 Heterochromatin Protein Promotes NHEJ by Direct Inhibition of Sae2[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/2021.05.26.445723.点此复制
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