Breast cancer type 1 susceptibility protein

Definition:

E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator.

References:

[1]. Cassandra J Vandenberg, et al. BRCA1-independent ubiquitination of FANCD2. Mol Cell. 2003 Jul;12(1):247-54. [Content Brief]

[2]. Lin Feng, et al. MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev. 2009 Mar 15;23(6):719-28. [Content Brief]

[3]. H Hiraike, et al. Identification of DBC1 as a transcriptional repressor for BRCA1. Br J Cancer. 2010 Mar 16;102(6):1061-7. [Content Brief]

[4]. J S Lee, et al. hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature. 2000 Mar 9;404(6774):201-4. [Content Brief]

[5]. Xiaochun Yu, et al. BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP. Genes Dev. 2006 Jul 1;20(13):1721-6. [Content Brief]

[6]. Ronit I Yarden, et al. BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. Nat Genet. 2002 Mar;30(3):285-9. [Content Brief]

[7]. Bin Wang, et al. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 2007 May 25;316(5828):1194-8. [Content Brief]

[8]. Karen Moreau, et al. BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase. J Biol Chem. 2006 Feb 10;281(6):3172-81. [Content Brief]

[9]. K L Lorick, et al. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11364-9. [Content Brief]

[10]. Shirley M H Sy, et al. PALB2 is an integral component of the BRCA complex required for homologous recombination repair. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7155-60. [Content Brief]

[11]. Satish Sankaran, et al. Aurora-A kinase regulates breast cancer associated gene 1 inhibition of centrosome-dependent microtubule nucleation. Cancer Res. 2007 Dec 1;67(23):11186-94. [Content Brief]

[12]. Foon Wu-Baer, et al. The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function. Mol Cell Biol. 2010 Jun;30(11):2787-98. [Content Brief]

[13]. Bo Xu, et al. Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer Res. 2002 Aug 15;62(16):4588-91. [Content Brief]

[14]. Foon Wu-Baer, et al. The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin. J Biol Chem. 2003 Sep 12;278(37):34743-6. [Content Brief]

[15]. Joanna R Morris, et al. BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Hum Mol Genet. 2004 Apr 15;13(8):807-17. [Content Brief]

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