MDC1

Mediator of DNA-damage checkpoint 1
PDB rendering based on 2ado.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2ADO, 2AZM, 2ETX, 3K05, 3UMZ, 3UN0, 3UNM, 3UNN, 3UNN, 3UOT, 3UOT
Identifiers
Symbols	MDC1; NFBD1
External IDs	OMIM: 607593 MGI: 3525201 HomoloGene: 67092 GeneCards: MDC1 Gene
Gene Ontology Molecular function • protein binding • protein C-terminus binding • FHA domain binding Cellular component • intracellular • nucleus • nucleoplasm • nucleolus • focal adhesion Biological process • double-strand break repair via homologous recombination • DNA repair • double-strand break repair • cell cycle • intra-S DNA damage checkpoint Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9656	240087
Ensembl	ENSG00000137337	ENSMUSG00000061607
UniProt	Q14676	Q5PSV9
RefSeq (mRNA)	NM_014641.2	NM_001010833.2
RefSeq (protein)	NP_055456.2	NP_001010833.2
Location (UCSC)	Chr 6: 30.67 – 30.69 Mb	Chr 17: 35.98 – 36 Mb
PubMed search	[1]	[2]

Mediator of DNA damage checkpoint protein 1 is a protein that in humans is encoded by the MDC1 gene.

The protein encoded by this gene 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.

Interactions

MDC1 has been shown to interact with MRE11A, H2AFX and CHEK2.

Further reading

• Stucki M, Jackson SP (2005). "MDC1/NFBD1: a key regulator of the DNA damage response in higher eukaryotes". DNA Repair (Amst.) 3 (8–9): 953–957. doi:10.1016/j.dnarep.2004.03.007. PMID 15279781. 
• Nagase T, Seki N, Ishikawa K et al (1996). "Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res. 3 (1): 17–24. doi:10.1093/dnares/3.1.17. PMID 8724849. 
• Shang YL, Bodero AJ, Chen PL (2003). "NFBD1, a novel nuclear protein with signature motifs of FHA and BRCT, and an internal 41-amino acid repeat sequence, is an early participant in DNA damage response". J. Biol. Chem. 278 (8): 6323–6329. doi:10.1074/jbc.M210749200. PMID 12475977. 
• Strausberg RL, Feingold EA, Grouse LH et al (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Xu X, Stern DF (2003). "NFBD1/KIAA0170 is a chromatin-associated protein involved in DNA damage signaling pathways". J. Biol. Chem. 278 (10): 8795–8803. doi:10.1074/jbc.M211392200. PMID 12499369. 
• Peng A, Chen PL (2003). "NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage". J. Biol. Chem. 278 (11): 8873–8876. doi:10.1074/jbc.C300001200. PMID 12551934. 
• Goldberg M, Stucki M, Falck J et al (2003). "MDC1 is required for the intra-S-phase DNA damage checkpoint". Nature 421 (6926): 952–956. doi:10.1038/nature01445. PMID 12607003. 
• Lou Z, Minter-Dykhouse K, Wu X, Chen J (2003). "MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways". Nature 421 (6926): 957–961. doi:10.1038/nature01447. PMID 12607004. 
• Lou Z, Chini CC, Minter-Dykhouse K, Chen J (2003). "Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control". J. Biol. Chem. 278 (16): 13599–13602. doi:10.1074/jbc.C300060200. PMID 12611903. 
• Xu X, Stern DF (2003). "NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors". FASEB J. 17 (13): 1842–1848. doi:10.1096/fj.03-0310com. PMID 14519663. 
• Mungall AJ, Palmer SA, Sims SK et al (2003). "The DNA sequence and analysis of human chromosome 6". Nature 425 (6960): 805–811. doi:10.1038/nature02055. PMID 14574404. 
• Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–52918. doi:10.1074/jbc.C300407200. PMID 14578343. 
• Mochan TA, Venere M, DiTullio RA, Halazonetis TD (2004). "53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response to DNA damage". Cancer Res. 63 (24): 8586–91. PMID 14695167. 
• Lukas C, Melander F, Stucki M et al (2005). "Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention". EMBO J. 23 (13): 2674–2683. doi:10.1038/sj.emboj.7600269. PMC 449779. PMID 15201865. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=449779. 
• Beausoleil SA, Jedrychowski M, Schwartz D et al (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–12135. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514446. 
• Lou Z, Chen BP, Asaithamby A et al (2004). "MDC1 regulates DNA-PK autophosphorylation in response to DNA damage". J. Biol. Chem. 279 (45): 46359–46362. doi:10.1074/jbc.C400375200. PMID 15377652. 
• Polci R, Peng A, Chen PL et al (2005). "NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response". Cancer Res. 64 (24): 8800–8803. doi:10.1158/0008-5472.CAN-04-2243. PMID 15604234.