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

V Savic, B Yin, NL Maas, AL Bredemeyer… - Molecular cell, 2009 - cell.com
V Savic, B Yin, NL Maas, AL Bredemeyer, AC Carpenter, BA Helmink, KS Yang-Iott…
Molecular cell, 2009cell.com
A hallmark of the cellular response to DNA double-strand breaks (DSBs) is histone H2AX
phosphorylation in chromatin to generate γ-H2AX. Here, we demonstrate that γ-H2AX
densities increase transiently along DNA strands as they are broken and repaired in G1
phase cells. The region across which γ-H2AX forms does not spread as DSBs persist; rather,
γ-H2AX densities equilibrate at distinct levels within a fixed distance from DNA ends.
Although both ATM and DNA-PKcs generate γ-H2AX, only ATM promotes γ-H2AX formation …
Summary
A hallmark of the cellular response to DNA double-strand breaks (DSBs) is histone H2AX phosphorylation in chromatin to generate γ-H2AX. Here, we demonstrate that γ-H2AX densities increase transiently along DNA strands as they are broken and repaired in G1 phase cells. The region across which γ-H2AX forms does not spread as DSBs persist; rather, γ-H2AX densities equilibrate at distinct levels within a fixed distance from DNA ends. Although both ATM and DNA-PKcs generate γ-H2AX, only ATM promotes γ-H2AX formation to maximal distance and maintains γ-H2AX densities. MDC1 is essential for γ-H2AX formation at high densities near DSBs, but not for generation of γ-H2AX over distal sequences. Reduced H2AX levels in chromatin impair the density, but not the distance, of γ-H2AX formed. Our data suggest that H2AX fuels a γ-H2AX self-reinforcing mechanism that retains MDC1 and activated ATM in chromatin near DSBs and promotes continued local phosphorylation of H2AX.
cell.com
以上显示的是最相近的搜索结果。 查看全部搜索结果