| Literature DB >> 19450528 |
Velibor Savic1, Bu Yin, Nancy L Maas, Andrea L Bredemeyer, Andrea C Carpenter, Beth A Helmink, Katherine S Yang-Iott, Barry P Sleckman, Craig H Bassing.
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.Entities:
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Year: 2009 PMID： 19450528 PMCID： PMC2744111 DOI： 10.1016/j.molcel.2009.04.012
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970