MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways

@article{Lou2003MDC1IC,
  title={MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways},
  author={Zhenkun Lou and Katherine Minter-Dykhouse and Xianglin Wu and Junjie Chen},
  journal={Nature},
  year={2003},
  volume={421},
  pages={957-961}
}
Forkhead-homology-associated (FHA) domains function as protein–protein modules that recognize phosphorylated serine/threonine motifs. Interactions between FHA domains and phosphorylated proteins are thought to have essential roles in the transduction of DNA damage signals; however, it is unclear how FHA-domain-containing proteins participate in mammalian DNA damage responses. Here we report that a FHA-domain-containing protein—mediator of DNA damage checkpoint protein 1 (MDC1; previously known… 
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This study uncovers an ID3-dependent mechanism of recruitment of MDC1 to DNA damage sites and suggests that the ID3–MDC1 interaction is crucial for DDR.
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TLDR
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MDC1 Regulates DNA-PK Autophosphorylation in Response to DNA Damage*
TLDR
Results suggest that the MDC1 repeat region is involved in protein-protein interaction with DNA-PKcs/Ku, and M DC1 regulates DNA damage repair by influencing DNA- PK autophosphorylation.
Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage
TLDR
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The DNA Damage Response Mediator MDC1 Directly Interacts with the Anaphase-promoting Complex/Cyclosome*
TLDR
A link between the cellular response to DNA damage and cell cycle regulation is revealed, suggesting that MDC1, known to have a role in checkpoint regulation, executes part of this role by binding the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that controls the cell cycle.
Regulatory motifs in Chk1
TLDR
It is shown here that Chk1 homologs possess a kinase-associated 1 (KA1) domain that possesses residues previously implicated in Chk 1 auto-inhibition, and all Chk2 homologys have a small and highly conserved C-terminal extension (CTE domain), which may provide alternative targets to the ATP-binding pocket on which to dock Ch k1 inhibitors as anticancer therapeutics.
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