Breast cancer type 2 susceptibility protein

Definition:

Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination.

References:

[1]. Ryan B Jensen, et al. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature. 2010 Oct 7;467(7316):678-83. [Content Brief]

[2]. Shobbir Hussain, et al. Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. Hum Mol Genet. 2004 Jun 15;13(12):1241-8. [Content Brief]

[3]. XiaoZhe Wang, et al. Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Mol Cell Biol. 2004 Jul;24(13):5850-62. [Content Brief]

[4]. Vaibhav Bhatia, et al. BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2. Nature. 2014 Jul 17;511(7509):362-5. [Content Brief]

[5]. Jie Liu, et al. Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA. Nat Struct Mol Biol. 2010 Oct;17(10):1260-2. [Content Brief]

[6]. Hui-Feng Wang, et al. BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with the Rho effector kinase ROCK2. Cancer Res. 2011 Jan 1;71(1):68-77. [Content Brief]

[7]. Tina Thorslund, et al. The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA. Nat Struct Mol Biol. 2010 Oct;17(10):1263-5. [Content Brief]

[8]. Kajal Biswas, et al. A comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia using mouse ES cell-based assay. Blood. 2011 Sep 1;118(9):2430-42. [Content Brief]

[9]. E M Bahassi, et al. The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage. Oncogene. 2008 Jun 26;27(28):3977-85. [Content Brief]

[10]. Rémi Buisson, et al. Breast cancer proteins PALB2 and BRCA2 stimulate polymerase η in recombination-associated DNA synthesis at blocked replication forks. Cell Rep. 2014 Feb 13;6(3):553-64. [Content Brief]

[11]. Akihiro Ohashi, et al. Fanconi anemia complementation group D2 (FANCD2) functions independently of BRCA2- and RAD51-associated homologous recombination in response to DNA damage. J Biol Chem. 2005 Apr 15;280(15):14877-83. [Content Brief]

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