Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining
| Autor: | Jac A. Nickoloff, Mark A. Brenneman, Montaser Shaheen, Robert Hromas, Suk Hee Lee, Leyma P. De Haro, Elizabeth A. Williamson, Krishnan Radhakrishnan, Justin Wray, Sheema Fnu |
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| Rok vydání: | 2010 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Time Factors DNA Repair DNA repair genetic processes Biology Histones Histone H3 Cell Line Tumor Histone methylation DNA Repair Protein Histone H2A Humans DNA Breaks Double-Stranded Cancer epigenetics Deoxyribonucleases Type II Site-Specific Ku Autoantigen Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Lysine fungi Antigens Nuclear DNA Restriction Enzymes Histone-Lysine N-Methyltransferase DNA Methylation Models Theoretical Biological Sciences Molecular biology Non-homologous end joining DNA-Binding Proteins Gene Expression Regulation Neoplastic enzymes and coenzymes (carbohydrates) Histone methyltransferase health occupations biological phenomena cell phenomena and immunity Dimerization |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 108(2) |
| ISSN: | 1091-6490 |
| Popis: | Given its significant role in the maintenance of genomic stability, histone methylation has been postulated to regulate DNA repair. Histone methylation mediates localization of 53BP1 to a DNA double-strand break (DSB) during homologous recombination repair, but a role in DSB repair by nonhomologous end-joining (NHEJ) has not been defined. By screening for histone methylation after DSB induction by ionizing radiation we found that generation of dimethyl histone H3 lysine 36 (H3K36me2) was the major event. Using a novel human cell system that rapidly generates a single defined DSB in the vast majority of cells, we found that the DNA repair protein Metnase (also SETMAR), which has a SET histone methylase domain, localized to an induced DSB and directly mediated the formation of H3K36me2 near the induced DSB. This dimethylation of H3K36 improved the association of early DNA repair components, including NBS1 and Ku70, with the induced DSB, and enhanced DSB repair. In addition, expression of JHDM1a (an H3K36me2 demethylase) or histone H3 in which K36 was mutated to A36 or R36 to prevent H3K36me2 formation decreased the association of early NHEJ repair components with an induced DSB and decreased DSB repair. Thus, these experiments define a histone methylation event that enhances DNA DSB repair by NHEJ. |
| Databáze: | OpenAIRE |
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