ATM phosphorylates MDC1

Stable Identifier
R-HSA-5693536
Type
Reaction [transition]
Species
Homo sapiens
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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.

Literature References
PubMed ID Title Journal Year
12607003 MDC1 is required for the intra-S-phase DNA damage checkpoint.

Goldberg, M, Stucki, M, D'Amours, D, Rahman, D, Pappin, D

Nature 2003
18006705 Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase

Kolas, NK, Chapman, JR, Nakada, S, Ylanko, J, Chahwan, R, Sweeney, FD, Panier, S, Mendez, M, Wildenhain, J, Thomson, TM, Pelletier, L, Jackson, SP, Durocher, D

Science 2007
22234877 Structural mechanism of the phosphorylation-dependent dimerization of the MDC1 forkhead-associated domain

Liu, J, Luo, S, Zhao, H, Liao, J, Li, J, Yang, C, Xu, B, Stern, DF, Xu, X, Ye, K

Nucleic Acids Res. 2012
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Catalyst Activity
Title
protein serine/threonine kinase activity of DNA DSBs:p-MRN:p-S1981,Ac-K3016-ATM:KAT5:p-S139-H2AFX-Nucleosome:MDC1 [nucleoplasm]
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Orthologous Events
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