A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.

Mutations are a major driving force of evolution and genetic disease. In eukaryotes, mutations are produced in the chromatin environment, but the impact of chromatin on mutagenesis is poorly understood. Previous studies have determined that in yeast Saccharomyces cerevisiae, Rtt109-dependent acetyla...

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Autores principales: Lyudmila Y Kadyrova, Tony M Mertz, Yu Zhang, Matthew R Northam, Ziwei Sheng, Kirill S Lobachev, Polina V Shcherbakova, Farid A Kadyrov
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/1e025a27b5d0423a8048951072262292
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spelling oai:doaj.org-article:1e025a27b5d0423a80489510722622922021-11-18T06:21:40ZA reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.1553-73901553-740410.1371/journal.pgen.1003899https://doaj.org/article/1e025a27b5d0423a80489510722622922013-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24204308/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Mutations are a major driving force of evolution and genetic disease. In eukaryotes, mutations are produced in the chromatin environment, but the impact of chromatin on mutagenesis is poorly understood. Previous studies have determined that in yeast Saccharomyces cerevisiae, Rtt109-dependent acetylation of histone H3 on K56 is an abundant modification that is introduced in chromatin in S phase and removed by Hst3 and Hst4 in G2/M. We show here that the chromatin deacetylation on histone H3 K56 by Hst3 and Hst4 is required for the suppression of spontaneous gross chromosomal rearrangements, base substitutions, 1-bp insertions/deletions, and complex mutations. The rate of base substitutions in hst3Δ hst4Δ is similar to that in isogenic mismatch repair-deficient msh2Δ mutant. We also provide evidence that H3 K56 acetylation by Rtt109 is important for safeguarding DNA from small insertions/deletions and complex mutations. Furthermore, we reveal that both the deacetylation and acetylation on histone H3 K56 are involved in mutation avoidance mechanisms that cooperate with mismatch repair and the proofreading activities of replicative DNA polymerases in suppressing spontaneous mutagenesis. Our results suggest that cyclic acetylation and deacetylation of chromatin contribute to replication fidelity and play important roles in the protection of nuclear DNA from diverse spontaneous mutations.Lyudmila Y KadyrovaTony M MertzYu ZhangMatthew R NorthamZiwei ShengKirill S LobachevPolina V ShcherbakovaFarid A KadyrovPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 10, p e1003899 (2013)
institution DOAJ
collection DOAJ
language EN
topic Genetics
QH426-470
spellingShingle Genetics
QH426-470
Lyudmila Y Kadyrova
Tony M Mertz
Yu Zhang
Matthew R Northam
Ziwei Sheng
Kirill S Lobachev
Polina V Shcherbakova
Farid A Kadyrov
A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.
description Mutations are a major driving force of evolution and genetic disease. In eukaryotes, mutations are produced in the chromatin environment, but the impact of chromatin on mutagenesis is poorly understood. Previous studies have determined that in yeast Saccharomyces cerevisiae, Rtt109-dependent acetylation of histone H3 on K56 is an abundant modification that is introduced in chromatin in S phase and removed by Hst3 and Hst4 in G2/M. We show here that the chromatin deacetylation on histone H3 K56 by Hst3 and Hst4 is required for the suppression of spontaneous gross chromosomal rearrangements, base substitutions, 1-bp insertions/deletions, and complex mutations. The rate of base substitutions in hst3Δ hst4Δ is similar to that in isogenic mismatch repair-deficient msh2Δ mutant. We also provide evidence that H3 K56 acetylation by Rtt109 is important for safeguarding DNA from small insertions/deletions and complex mutations. Furthermore, we reveal that both the deacetylation and acetylation on histone H3 K56 are involved in mutation avoidance mechanisms that cooperate with mismatch repair and the proofreading activities of replicative DNA polymerases in suppressing spontaneous mutagenesis. Our results suggest that cyclic acetylation and deacetylation of chromatin contribute to replication fidelity and play important roles in the protection of nuclear DNA from diverse spontaneous mutations.
format article
author Lyudmila Y Kadyrova
Tony M Mertz
Yu Zhang
Matthew R Northam
Ziwei Sheng
Kirill S Lobachev
Polina V Shcherbakova
Farid A Kadyrov
author_facet Lyudmila Y Kadyrova
Tony M Mertz
Yu Zhang
Matthew R Northam
Ziwei Sheng
Kirill S Lobachev
Polina V Shcherbakova
Farid A Kadyrov
author_sort Lyudmila Y Kadyrova
title A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.
title_short A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.
title_full A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.
title_fullStr A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.
title_full_unstemmed A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.
title_sort reversible histone h3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/1e025a27b5d0423a8048951072262292
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