Hst3 and Hst4 histone deacetylases regulate replicative lifespan by preventing genome instability in Saccharomyces cerevisiae

Genes Cells. 2011 Apr;16(4):467-77. doi: 10.1111/j.1365-2443.2011.01493.x. Epub 2011 Mar 15.


The acetylation of histone H3 on lysine 56 (H3-K56) occurs during S phase and contributes to the processes of DNA damage repair and histone gene transcription. Hst3 and Hst4 have been implicated in the removal of histone H3-K56 acetylation in Saccharomyces cerevisiae. Here, we show that Hst3 and Hst4 regulate the replicative lifespan of S. cerevisiae mother cells. An hst3Δ hst4Δ double-mutant strain, in which acetylation of histone H3-K56 persists throughout the genome during the cell cycle, exhibits genomic instability, which is manifested by a loss of heterozygosity with cell aging. Furthermore, we show that in the absence of other proteins Hst3 and Hst4 can deacetylate nucleosomal histone H3-K56 in a nicotinamide adenine dinucleotide(NAD)(+) -dependent manner. Our results suggest that Hst3 and Hst4 regulate replicative lifespan through their ability to deacetylate histone H3-K56 to minimize genomic instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genomic Instability
  • Histone Deacetylases / genetics
  • Histone Deacetylases / physiology*
  • Histones / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • Sirtuin 2 / metabolism


  • Histones
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Hst3 protein, S cerevisiae
  • Hst4 protein, S cerevisiae
  • SIR2 protein, S cerevisiae
  • Sirtuin 2
  • Histone Deacetylases