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The chromatin remodeler Chd1 supports MRX and Exo1 functions in resection of DNA double-strand breaks
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...
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Published in: | PLoS genetics 2021-09, Vol.17 (9), p.e1009807-e1009807 |
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description | 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. |
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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34520455</pmid><doi>10.1371/journal.pgen.1009807</doi><orcidid>https://orcid.org/0000-0002-4096-714X</orcidid><orcidid>https://orcid.org/0000-0001-6131-0879</orcidid><orcidid>https://orcid.org/0000-0003-1726-2034</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adenosine triphosphatase Biology and life sciences Chromatin Chromatin remodeling Chromosomes DNA binding proteins DNA Breaks, Double-Stranded DNA damage DNA repair DNA-Binding Proteins - physiology Efficiency Evictions Exodeoxyribonucleases - metabolism Experiments Genes, Fungal Genetic research Histones Histones - isolation & purification Homologous recombination Medicine and Health Sciences MRE11 protein Nuclease Physical sciences Prostate cancer Proteins RNA polymerase Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae Proteins - physiology Single-stranded DNA Structure Yeast |
title | The chromatin remodeler Chd1 supports MRX and Exo1 functions in resection of DNA double-strand breaks |
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