Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin

Savic, Velibor, Yin, Bu, Maas, Nancy L, Bredemeyer, Andrea L, Carpenter, Andrea C, Helmink, Beth A, Yang-Iott, Katherine S, Sleckman, Barry P and Bassing, Craig H (2009) Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin. Molecular Cell, 34 (3). pp. 298-310. ISSN 1097-2765

Full text not available from this repository.

Abstract

A hallmark of the cellular response to DNA double-strand breaks (DSBs) is histone H2AX phosphorylation in chromatin to generate gamma-H2AX. Here, we demonstrate that gamma-H2AX densities increase transiently along DNA strands as they are broken and repaired in G1 phase cells. The region across which gamma-H2AX forms does not spread as DSBs persist; rather, gamma-H2AX densities equilibrate at distinct levels within a fixed distance from DNA ends. Although both ATM and DNA-PKcs generate gamma-H2AX, only ATM promotes gamma-H2AX formation to maximal distance and maintains gamma-H2AX densities. MDC1 is essential for gamma-H2AX formation at high densities near DSBs, but not for generation of gamma-H2AX over distal sequences. Reduced H2AX levels in chromatin impair the density, but not the distance, of gamma-H2AX formed. Our data suggest that H2AX fuels a gamma-H2AX self-reinforcing mechanism that retains MDC1 and activated ATM in chromatin near DSBs and promotes continued local phosphorylation of H2AX

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome
Q Science > QH Natural history > QH0301 Biology
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0460 Mutations
Depositing User: Velibor Savic
Date Deposited: 11 Feb 2013 14:27
Last Modified: 14 May 2015 09:35
URI: http://sro.sussex.ac.uk/id/eprint/43581
📧 Request an update