MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways
作者： Zhenkun Lou , Katherine Minter-Dykhouse , Xianglin Wu , Junjie Chen
DOI: 10.1038/NATURE01447
关键词:
摘要: Forkhead-homology-associated (FHA) domains function as protein-protein modules that recognize phosphorylated serine/threonine motifs. Interactions between FHA and proteins are thought to have essential roles in the transduction of DNA damage signals; however, it is unclear how FHA-domain-containing participate mammalian responses. Here we report a protein-mediator checkpoint protein 1 (MDC1; previously known KIAA0170)--is involved MDC1 localizes sites breaks associates with CHK2 after damage. This association mediated by domain Thr 68 CHK2. Furthermore, an ATM/CHK2-dependent manner damage, suggesting may ATM-CHK2 pathway. Consistent this hypothesis, suppression expression results defective S-phase reduced apoptosis response which can be restored wild-type but not deleted domain. Suppression decreased p53 stabilization These suggest recruited through its activated CHK2, has critical role CHK2-mediated
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