MDC1

Mediator of DNA-damage checkpoint 1

PDB rendering based on 2ado.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsMDC1 ; NFBD1
External IDsOMIM: 607593 MGI: 3525201 HomoloGene: 67092 GeneCards: MDC1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez9656240087
EnsemblENSG00000137337ENSMUSG00000061607
UniProtQ14676Q5PSV9
RefSeq (mRNA)NM_014641NM_001010833
RefSeq (protein)NP_055456NP_001010833
Location (UCSC)Chr 6:
30.67 – 30.69 Mb		Chr 17:
35.84 – 35.86 Mb
PubMed search

Mediator of DNA damage checkpoint protein 1 is a protein that in humans is encoded by the MDC1 gene.[1][2][3]

Function

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.[3]

Interactions

MDC1 has been shown to interact with:

References

  1. ↑ Ozaki T, Nagase T, Ichimiya S, Seki N, Ohiri M, Nomura N et al. (Sep 2000). "NFBD1/KIAA0170 is a novel nuclear transcriptional transactivator with BRCT domain". DNA Cell Biol 19 (8): 475–485. doi:10.1089/10445490050128403. PMID 10975465.
  2. ↑ 2.0 2.1 Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ (Feb 2003). "MDC1 is a mediator of the mammalian DNA damage checkpoint". Nature 421 (6926): 961–966. doi:10.1038/nature01446. PMID 12607005.
  3. ↑ 3.0 3.1 "Entrez Gene: MDC1 mediator of DNA damage checkpoint 1".
  4. ↑ Lou Z, Minter-Dykhouse K, Wu X, Chen J (Feb 2003). "MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways". Nature 421 (6926): 957–61. doi:10.1038/nature01447. PMID 12607004.
  5. ↑ 5.0 5.1 Xu X, Stern DF (Oct 2003). "NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors". FASEB J. 17 (13): 1842–8. doi:10.1096/fj.03-0310com. PMID 14519663.

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, Tanaka A, Nomura N (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.
  • 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, D'Amours D, Rahman D, Pappin D 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.
  • 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, Falck J, Bekker-Jensen S, Goldberg 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.
  • Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J 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. Vancouver style error (help)
  • Lou Z, Chen BP, Asaithamby A, Minter-Dykhouse K, Chen DJ, Chen J (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, Riley DJ, Chen Y (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.