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首页> 外文期刊>Molecular cell >Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin.
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Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin.

机译：沿着断裂的DNA链形成动态γ-H2AX结构域的过程明显受ATM和MDC1的调节，并取决于染色质中的H2AX密度。

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摘要

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.
机译：细胞对DNA双链断裂（DSB）的反应的标志是染色质中的组蛋白H2AX磷酸化以生成γ-H2AX。在这里，我们证明了γ-H2AX密度沿着DNA链瞬时增加，因为它们在G1期细胞中断裂和修复。随着DSB的持续，γ-H2AX形成的区域不会扩散;相反，γ-H2AX密度在距DNA末端固定距离内的不同水平达到平衡。尽管ATM和DNA-PKcs都生成γ-H2AX，但只有ATM可以将γ-H2AX的形成促进到最大距离并保持γ-H2AX的密度。 MDC1对于在DSB附近以高密度形成γ-H2AX是必不可少的，但对于在远端序列上生成γ-H2AX而言则不是必需的。染色质中H2AX含量降低会影响所形成的γ-H2AX的密度，但不会影响距离。我们的数据表明，H2AX为γ-H2AX自增强机制提供了燃料，该机制将MDC1和活化的ATM保留在DSB附近的染色质中，并促进H2AX的持续局部磷酸化。

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