Mediator of damage checkpoint

The cell is equipped with a number of critical checkpoint proteins that ensure the integrity of the genome and the coordination of DNA repair and cell cycle pathways. In the February 27 Nature, three papers describe the role of the mediator of DNA damage checkpoint protein 1 (MDC1) in the DNA damage response. Michal Goldberg and colleagues identified the MDC1 protein during an immunoaffinity purification of the MRE11 repair complex (Nature, 421:952-956, February 27, 2003). Zhenken Lou and colleagues (Nature, 421:957-961, February 27, 2003) and Grant S. Stewart and colleagues (Nature, 421:961-966, February 27, 2003) identified MDC1 by searching for motifs commonly found in DNA repair proteins.

MDC1 is a large protein with two carboxy-terminal BRCT (BRCA1 carboxy-terminal) repeats and an amino-terminal phospho-binding motif called FHA (forkhead associated domain). The MDC1 protein becomes hyperphosphorylated after exposure to ionizing radiation and rapidly localizes to nuclear foci that contain other repair proteins ...