Reactome | ATM phosphorylates MDC1

ATM phosphorylates MDC1

Stable Identifier

R-HSA-5693536

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
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
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
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