Sir3 heterochromatin protein promotes non-homologous end joining by direct inhibition of Sae2.

Autor:	Bordelet H; Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France.; Régulation spatiale des génomes, Institut Pasteur, CNRS UMR3525, Paris, France., Costa R; Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France., Brocas C; Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France., Dépagne J; CIGEx platform. Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France., Veaute X; CIGEx platform. Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France., Busso D; CIGEx platform. Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France., Batté A; Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France.; Center for Integrative Genomics, Bâtiment Génopode, University of Lausanne, Lausanne, Switzerland., Guérois R; Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France., Marcand S; Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France., Dubrana K; Université de Paris and Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, France.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2022 Jan 04; Vol. 41 (1), pp. e108813. Date of Electronic Publication: 2021 Nov 24.
DOI:	10.15252/embj.2021108813
Abstrakt:	Heterochromatin is a conserved feature of eukaryotic chromosomes, with central roles in gene expression regulation and maintenance of genome stability. How heterochromatin proteins regulate DNA repair remains poorly described. In the yeast Saccharomyces cerevisiae, the silent information regulator (SIR) complex assembles heterochromatin-like chromatin at sub-telomeric chromosomal regions. SIR-mediated repressive chromatin limits DNA double-strand break (DSB) resection, thus protecting damaged chromosome ends during homologous recombination (HR). As resection initiation represents the crossroads between repair by non-homologous end joining (NHEJ) or HR, we asked whether SIR-mediated heterochromatin regulates NHEJ. We show that SIRs promote 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. Via physical interaction with the Sae2 protein, Sir3 impairs Sae2-dependent functions of the MRX (Mre11-Rad50-Xrs2) complex, thereby limiting Mre11-mediated resection, delaying MRX removal from DSB ends, and promoting NHEJ. (© 2021 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text