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

Authors

  • Mayumi Hachinohe,

    1. Graduate School of Life and Environmental Sciences, Initiative for the Promotion of Young Scientists’ Independent Research, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan
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  • Fumio Hanaoka,

    1. Department of Life Science, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima, Tokyo 171-8588, Japan
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  • Hiroshi Masumoto

    Corresponding author
    1. Graduate School of Life and Environmental Sciences, Initiative for the Promotion of Young Scientists’ Independent Research, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan
      himasumo@sakura.cc.tsukuba.ac.jp
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  • Communicated by: Katsuhiko Shirahige

himasumo@sakura.cc.tsukuba.ac.jp

Abstract

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.

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