BRCA2

 

Involved in DNA repair by homologous recombination. Regulates Rad51 function. Possible role in stabilizing stalled forks

 

 

Synonyms

Xrcc11 (hamster) (1)

FANCD1

Molecular weight

 

Biochemical properties

 

Motifs

•BRCT domains (8 copies) (2)

•Transcriptional activation domain at n terminus (3)

•nls

 

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)

 

 

Modifications

•Hyperphosphorylated in M via plk (9) (14)

•Phosphorylated (cdk) (15)

 

Structure

• with DSS (16)

 

Cellular location and expression

 

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

 

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.