Mediator Of DNA Damage Checkpoint Protein 1 (MDC1)

MDC1 contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 13 repetitions of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci.

MDC1 was hyperphosphorylated in an ATM-dependent manner and rapidly relocalized to nuclei foci containing the MRE11 complex, phosphorylated histone H2AX, and TP53BP1 .