BRCA2
Involved in DNA repair by homologous recombination. Regulates Rad51 function. Possible role in stabilizing stalled forks
Synonyms |
Xrcc11 (hamster) (1) FANCD1 |
Molecular weight |
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Biochemical properties |
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Motifs |
•BRCT domains (8 copies) (2) •Transcriptional activation domain at n terminus (3) •nls
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Protein interactions |
Mammals •Rad51 (4) (5) •Bccipa (6) •Dss1 (7) • Rpa (8) •Pcaf (9) •Emsy (10) •Palb2 (11) • DMC1 (12)
Complexes • Colocalises BRAF (2MDa), seen in chromosomes at start condensation (13)
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Modifications |
•Hyperphosphorylated in M via plk (9) (14) •Phosphorylated (cdk) (15)
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Structure |
• with DSS (16)
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Cellular location and expression |
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Other comments |
Mammals •Often mutated in familial breast and ovarian cancer syndrome. •Effects on HR repair (17) (18) •Seen at replication forks in hu (5) Role in stabilising stalled forks (19) • rat knockout (20) |
Revised by |
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Last edited |
15 April 08 |
1. Kraakman-van der Zwet,M., Overkamp,W.J., van Lange,R.E., Essers,J., van Duijn-Goedhart,A., Wiggers,I., Swaminathan,S., van Buul,P.P., Errami,A., Tan,R.T., Jaspers,N.G., Sharan,S.K., Kanaar,R. and Zdzienicka,M.Z. (2002) Brca2 (XRCC11) deficiency results in radioresistant DNA synthesis and a higher frequency of spontaneous deletions. Mol Cell Biol22, 669-679.
2. Kerr,P. and Ashworth,A. (2001) New complexities for BRCA1 and BRCA2. Curr Biol 11, R668-76.
3. Milner,J., Fuks,F., Hughes-Davies,L. and Kouzarides,T. (2000) The BRCA2 activation domain associates with and is phosphorylated by a cellular protein kinase. Oncogene 19, 4441-4445.
4. Davies,A.A., Masson,J.Y., McIlwraith,M.J., Stasiak,A.Z., Stasiak,A., Venkitaraman,A.R. and West,S.C. (2001) Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Mol Cell 7, 273-282.
5. Venkitaraman,A.R. (2001) Chromosome stability, DNA recombination and the BRCA2 tumour suppressor. Curr Opin Cell Biol 13, 338-343.
6. Liu,J., Yuan,Y., Huan,J. and Shen,Z. (2001) Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2. Oncogene 20, 336-345.
7. Yang,H., Jeffrey,P.D., Miller,J., Kinnucan,E., Sun,Y., Thoma,N.H., Zheng,N., Chen,P.L., Lee,W.H. and Pavletich,N.P. (2002) BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science 297, 1837-1848.
8. Wong,J.M., Ionescu,D. and Ingles,C.J. (2003) Interaction between BRCA2 and replication protein A is compromised by a cancer-predisposing mutation in BRCA2. Oncogene 22, 28-33.
9. Lin,H.R., Ting,N.S., Qin,J. and Lee,W.H. (2003) M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the dissociation of the BRCA2-P/CAF complex. J Biol Chem 278, 35979-35987.
10. Hughes-Davies,L., Huntsman,D., Ruas,M., Fuks,F., Bye,J., Chin,S.F., Milner,J., Brown,L.A., Hsu,F., Gilks,B., Nielsen,T., Schulzer,M., Chia,S., Ragaz,J., Cahn,A., Linger,L., Ozdag,H., Cattaneo,E., Jordanova,E.S., Schuuring,E., Yu,D.S., Venkitaraman,A., Ponder,B., Doherty,A., Aparicio,S., Bentley,D., Theillet,C., Ponting,C.P., Caldas,C. and Kouzarides,T. (2003) EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer. Cell 115, 523-535.
11. Xia,B., Sheng,Q., Nakanishi,K., Ohashi,A., Wu,J., Christ,N., Liu,X., Jasin,M., Couch,F.J. and Livingston,D.M. (2006) Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell 22, 719-729.
12. Thorslund,T., Esashi,F. and West,S.C. (2007) Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1. EMBO J 26, 2915-2922.
13. Marmorstein,L.Y., Kinev,A.V., Chan,G.K., Bochar,D.A., Beniya,H., Epstein,J.A., Yen,T.J. and Shiekhattar,R. (2001) A human BRCA2 complex containing a structural DNA binding component influences cell cycle progression. Cell 104, 247-257.
14. Lee,M., Daniels,M.J. and Venkitaraman,A.R. (2004) Phosphorylation of BRCA2 by the Polo-like kinase Plk1 is regulated by DNA damage and mitotic progression. Oncogene 23, 865-872.
15. Esashi,F., Christ,N., Gannon,J., Liu,Y., Hunt,T., Jasin,M. and West,S.C. (2005) CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair. Nature 434, 598-604.
16. Kojic,M., Yang,H., Kostrub,C.F., Pavletich,N.P. and Holloman,W.K. (2003) The BRCA2-interacting protein DSS1 is vital for DNA repair, recombination, and genome stability in Ustilago maydis. Mol Cell 12, 1043-1049.
17. Moynahan,M.E., Pierce,A.J. and Jasin,M. (2001) BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell 7, 263-272.
18. Tutt,A., Bertwistle,D., Valentine,J., Gabriel,A., Swift,S., Ross,G., Griffin,C., Thacker,J. and Ashworth,A. (2001) Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences. EMBO J 20, 4704-4716.
19. Lomonosov,M., Anand,S., Sangrithi,M., Davies,R. and Venkitaraman,A.R. (2003) Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein. Genes Dev 17, 3017-3022.
20. Cotroneo,M.S., Haag,J.D., Zan,Y., Lopez,C.C., Thuwajit,P., Petukhova,G.V., Camerini-Otero,R.D., Gendron-Fitzpatrick,A., Griep,A.E., Murphy,C.J., Dubielzig,R.R. and Gould,M.N. (2007) Characterizing a rat Brca2 knockout model. Oncogene26, 1626-1635.