Heterochromatin is refractory to γ-H2AX modification in yeast and mammals
| Autor: | Farokh Dotiwala, Michael J. Kruhlak, André Nussenzweig, Jung-Ae Kim, James E. Haber |
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| Rok vydání: | 2007 |
| Předmět: |
Chromatin Immunoprecipitation
Heterochromatin DNA damage cells Saccharomyces cerevisiae environment and public health Article Histones Mice 03 medical and health sciences 0302 clinical medicine Animals Phosphorylation Fluorescent Antibody Technique Indirect Research Articles Cells Cultured 030304 developmental biology Mammals 0303 health sciences biology Cell Biology Fibroblasts Embryo Mammalian biology.organism_classification Chromosomes Mammalian Molecular biology Telomere Chromatin enzymes and coenzymes (carbohydrates) Histone 030220 oncology & carcinogenesis Mutation biology.protein biological phenomena cell phenomena and immunity Chromatin immunoprecipitation Ataxia telangiectasia and Rad3 related DNA Damage |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Double-strand break (DSB) damage in yeast and mammalian cells induces the rapid ATM (ataxia telangiectasia mutated)/ATR (ataxia telangiectasia and Rad3 related)-dependent phosphorylation of histone H2AX (gamma-H2AX). In budding yeast, a single endonuclease-induced DSB triggers gamma-H2AX modification of 50 kb on either side of the DSB. The extent of gamma-H2AX spreading does not depend on the chromosomal sequences. DNA resection after DSB formation causes the slow, progressive loss of gamma-H2AX from single-stranded DNA and, after several hours, the Mec1 (ATR)-dependent spreading of gamma-H2AX to more distant regions. Heterochromatic sequences are only weakly modified upon insertion of a 3-kb silent HMR locus into a gamma-H2AX-covered region. The presence of heterochromatin does not stop the phosphorylation of chromatin more distant from the DSB. In mouse embryo fibroblasts, gamma-H2AX distribution shows that gamma-H2AX foci increase in size as chromatin becomes more accessible. In yeast, we see a high level of constitutive gamma-H2AX in telomere regions in the absence of any exogenous DNA damage, suggesting that yeast chromosome ends are transiently detected as DSBs. |
| Databáze: | OpenAIRE |
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