Heterochromatin is Refractory to Gamma-H2AX Modification in Yeast and Mammals

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2007 Jul 20

PMID 17635934

Citations 141

Authors

Jung-Ae Kim

Michael Kruhlak

Farokh Dotiwala

Andre Nussenzweig

James E Haber

Affiliations

Soon will be listed here.

Abstract

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.

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