Reaction: ATM phosphorylates MDC1
- in pathway: Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
The function of MDC1 in recruiting and retaining DNA repair proteins at the sites of DNA damage (Xu and Stern 2003, Stewart et al. 2003) is promoted by the ATM-mediated phosphorylation of MDC1 (Liu et al. 2012). Phosphorylation of MDC1 (NFBD1) by ATM at threonine residue T4 stabilizes otherwise unstable MDC1 homodimers by enabling in trans interaction of MDC1 FHA domains with phosphorylated N-terminal threonine residues (Goldberg et al. 2003, Liu et al. 2012). ATM also phosphorylates MDC1 on at least four threonine residues that match the consensus RNF8-binding sequence T-Q-X-F: T699, T719, T752, T765 (Kolas et al. 2007). Binding of the ubiquitin ligase RNF8 to ATM phosphorylated MDC1 is necessary for the recruitment of TP53BP1 and BRCA1 to DNA double-strand break (DSB) sites.
Reaction - small molecule participants:
ADP [nucleoplasm]
ATP [nucleoplasm]
Reactome.org reaction link: R-HSA-5693536
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Reaction input - small molecules:
ATP(4-)
Reaction output - small molecules:
ADP(3-)
Reactome.org link: R-HSA-5693536