Journal
EMBO JOURNAL
Volume 41, Issue 1, Pages -Publisher
WILEY
DOI: 10.15252/embj.2021108813
Keywords
DSB repair; heterochromatin; NHEJ; Sae2; Sir3
Categories
Funding
- Fondation pour la recherche medicale [DEP20131128535]
- European Research Council under the European Community [281287]
- Fondation ARC pour la Recherche sur le Cancer [PJA-20191209432]
- CEA Radiation biology programme
- EDF, Agence Nationale de la Recherche [ANR-18-CE12-0003]
- CEA-IRTELIS PhD programme
- European Research Council (ERC) [281287] Funding Source: European Research Council (ERC)
- Agence Nationale de la Recherche (ANR) [ANR-18-CE12-0003] Funding Source: Agence Nationale de la Recherche (ANR)
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Heterochromatin proteins, particularly the SIR complex, play a crucial role in regulating DNA repair pathways in yeast, with a focus on NHEJ. Sir3 interacts with the Sae2 protein to impair MRX complex functions, ultimately promoting NHEJ by limiting DNA resection and delaying MRX removal from DSB ends.
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.
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