title: Histone deacetylase 10 regulates DNA mismatch repair and may involve the deacetylation of MutS homolog 2.
abstract: MutS homolog 2 (MSH2) is an essential DNA mismatch repair (MMR) protein. It interacts with MSH6 or MSH3 to form the MutSα or MutSβ complex, respectively, which recognize base-base 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.
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Rangasudhagar
authors.initials: R
authors.lastname: Radhakrishnan
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: the Department of Pathology and Cell Biology, University of South Florida (USF) Morsani College of Medicine, Tampa, Florida 33612.
authors.forename: Shengyan
authors.initials: S
authors.lastname: Xiang
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida 33136, and.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Yuan
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Elphine
authors.initials: E
authors.lastname: Telles
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Jia
authors.initials: J
authors.lastname: Fang
authors.affiliation: Gastroenterology, and H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.affiliation: Gastroenterology, and H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612.
authors.forename: David
authors.initials: D
authors.lastname: Shibata
authors.affiliation: the Mass Spectrometry and Proteomics Resource Laboratory, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: William S
authors.initials: WS
authors.lastname: Lane
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida 33136, and.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Departments of Molecular Oncology and the Department of Pathology and Cell Biology, University of South Florida (USF) Morsani College of Medicine, Tampa, Florida 33612, xzhang1@health.usf.edu.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Departments of Molecular Oncology and ed.seto@moffitt.org.
authors.forename: Edward
authors.initials: E
authors.lastname: Seto
mesh_terms: D000107:Acetylation; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D053843:DNA Mismatch Repair; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D004247:DNA; C447828:HDAC10 protein, human; D006655:Histone Deacetylases; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein
keywords: DNA mismatch repair; histone acetylase; histone deacetylase (HDAC); histone deacetylase inhibitor (HDAC inhibitor) (HDI); post-translational modification (PTM)