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

Hélène Bordelet, Rafaël Costa, Clémentine Brocas, Jordane Dépagne, Xavier Veaute, Didier Busso, Amandine Batté, Raphaël Guérois, Stéphane Marcand, Karine Dubrana

The EMBO journal 2022 Jan 04

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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.

Citation

Hélène Bordelet, Rafaël Costa, Clémentine Brocas, Jordane Dépagne, Xavier Veaute, Didier Busso, Amandine Batté, Raphaël Guérois, Stéphane Marcand, Karine Dubrana. Sir3 heterochromatin protein promotes non-homologous end joining by direct inhibition of Sae2. The EMBO journal. 2022 Jan 04;41(1):e108813