The chromatin remodeler Chd1 supports MRX and Exo1 functions in resection of DNA double-strand breaks

Author:

Gnugnoli MarcoORCID,Casari ErikaORCID,Longhese Maria PiaORCID

Abstract

Repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) requires that the 5’-terminated DNA strands are resected to generate single-stranded DNA overhangs. This process is initiated by a short-range resection catalyzed by the MRX (Mre11-Rad50-Xrs2) complex, which is followed by a long-range step involving the nucleases Exo1 and Dna2. Here we show that the Saccharomyces cerevisiae ATP-dependent chromatin-remodeling protein Chd1 participates in both short- and long-range resection by promoting MRX and Exo1 association with the DSB ends. Furthermore, Chd1 reduces histone occupancy near the DSB ends and promotes DSB repair by HR. All these functions require Chd1 ATPase activity, supporting a role for Chd1 in the opening of chromatin at the DSB site to facilitate MRX and Exo1 processing activities.

Funder

Fondazione Italiana per la Ricerca sul Cancro

Ministero dell’Istruzione, dell’Università e della Ricerca

Italian Ministry of University and Research

Publisher

Public Library of Science (PLoS)

Subject

Cancer Research,Genetics(clinical),Genetics,Molecular Biology,Ecology, Evolution, Behavior and Systematics

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