A Reversible Histone H3 Acetylation Cooperates with Mismatch Repair and Replicative Polymerases in Maintaining Genome Stability

Lyudmila Y. Kadyrova, Tony M. Mertz, Yu Zhang, Matthew R. Northam, Ziwei Sheng, Kirill S. Lobachev, Polina V Shcherbakova, Farid A. Kadyrov

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere1003899
JournalPLoS genetics
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

DNA Mismatch Repair
Genomic Instability
acetylation
Acetylation
histones
Histones
repair
Chromatin
mutation
genome
chromatin
INDEL Mutation
Mutation
Mutagenesis
DNA
mutagenesis
substitution
Inborn Genetic Diseases
DNA-Directed DNA Polymerase
Eukaryota

ASJC Scopus subject areas

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

Cite this

Kadyrova, L. Y., Mertz, T. M., Zhang, Y., Northam, M. R., Sheng, Z., Lobachev, K. S., ... Kadyrov, F. A. (2013). A Reversible Histone H3 Acetylation Cooperates with Mismatch Repair and Replicative Polymerases in Maintaining Genome Stability. PLoS genetics, 9(10), [e1003899]. https://doi.org/10.1371/journal.pgen.1003899

A Reversible Histone H3 Acetylation Cooperates with Mismatch Repair and Replicative Polymerases in Maintaining Genome Stability. / Kadyrova, Lyudmila Y.; Mertz, Tony M.; Zhang, Yu; Northam, Matthew R.; Sheng, Ziwei; Lobachev, Kirill S.; Shcherbakova, Polina V; Kadyrov, Farid A.

In: PLoS genetics, Vol. 9, No. 10, e1003899, 01.10.2013.

Research output: Contribution to journalArticle

Kadyrova, Lyudmila Y. ; Mertz, Tony M. ; Zhang, Yu ; Northam, Matthew R. ; Sheng, Ziwei ; Lobachev, Kirill S. ; Shcherbakova, Polina V ; Kadyrov, Farid A. / A Reversible Histone H3 Acetylation Cooperates with Mismatch Repair and Replicative Polymerases in Maintaining Genome Stability. In: PLoS genetics. 2013 ; Vol. 9, No. 10.
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