Histone deacetylase 10 regulates DNA mismatch repair and may involve the deacetylation of MutS homolog 2

Rangasudhagar Radhakrishnan, Yixuan Li, Shengyan Xiang, Fenghua Yuan, Zhigang Yuan, Elphine Telles, Jia Fang, Domenico Coppola, David Shibata, William S. Lane, Yanbin Zhang, Xiaohong Zhang, Edward Seto

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

MutS homolog 2 (MSH2) is an essentialDNAmismatch repair (MMR) protein. It interacts with MSH6 or MSH3 to form the MutSα or MutSβ complex, respectively, which recognize basebase mispairs and insertions/deletions and initiate the repair process. Mutation or dysregulation of MSH2 causes genomic instability that can lead to cancer. MSH2 is acetylated at its C terminus, and histone deacetylase (HDAC6) deacetylates MSH2. However, whether other regions of MSH2 can be acetylated and whether other histone deacetylases (HDACs) and histone acetyltransferases (HATs) are involved in MSH2 deacetylation/acetylation is unknown. Here, we report that MSH2 can be acetylated at Lys-73 near the N terminus. Lys-73 is highly conserved across many species. Although several Class I and II HDACs interact with MSH2, HDAC10 is the major enzyme that deacetylates MSH2 at Lys-73. Histone acetyltransferase HBO1 might acetylate this residue. HDAC10 overexpression in HeLa cells stimulates cellular DNA MMR activity, whereas HDAC10 knockdown decreases DNA MMR activity. Thus, our study identifies an HDAC10-mediated regulatory mechanism controlling the DNA mismatch repair function of MSH2.

Original languageEnglish (US)
Pages (from-to)22795-22804
Number of pages10
JournalJournal of Biological Chemistry
Volume290
Issue number37
DOIs
StatePublished - Sep 11 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Radhakrishnan, R., Li, Y., Xiang, S., Yuan, F., Yuan, Z., Telles, E., Fang, J., Coppola, D., Shibata, D., Lane, W. S., Zhang, Y., Zhang, X., & Seto, E. (2015). Histone deacetylase 10 regulates DNA mismatch repair and may involve the deacetylation of MutS homolog 2. Journal of Biological Chemistry, 290(37), 22795-22804. https://doi.org/10.1074/jbc.M114.612945