Histone Deacetylase 10 Regulates DNA Mismatch Repair and May Involve the Deacetylation of MutS Homolog 2
| Autor: | Xiaohong Zhang, Rangasudhagar Radhakrishnan, Shengyan Xiang, Zhigang Yuan, Elphine Telles, David Shibata, Domenico Coppola, William S. Lane, Edward Seto, Fenghua Yuan, Yanbin Zhang, Yixuan Li, Jia Fang |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities DNA and Chromosomes DNA Mismatch Repair Biochemistry Histone Deacetylases Histone H2A Humans Histone code neoplasms Molecular Biology MutS Homolog 2 Protein Histone deacetylase 5 biology Histone deacetylase 2 nutritional and metabolic diseases Acetylation DNA Cell Biology Histone acetyltransferase Molecular biology digestive system diseases MSH3 biology.protein Histone deacetylase HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 290:22795-22804 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.612945 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|