Overview:

The breast cancer susceptibility protein BRCA1 is responsible for repairing DNA damage, controlling the cell cycle, transcriptional regulation, ubiquitination and maintaining genomic stability. BRCA1 interacts with several protein complexes through interactions with different adaptor molecules. For example, BRCA1 is a component of the RNA polymerase II holoenzyme (PolII) (1). Because of its role in maintaining DNA fidelity, mutations that affect the subcellular localization of BRCA1 can lead to cancer predisposition (2). BRCA1 is most commonly associated with breast cancer, but it is also implicated other cancers such as ovarian cancer. BRCA1 is phosphorylated at Ser988 after DNA damage and phosphorylated at Ser1423/1524 in response to radiation exposure (3,4).

References:

1. Scully, R. et al: BRCA1 is a component of the RNA polymerase II holoenzyme. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5605-10.

2. Chen, Y. et al: Aberrant subcellular localization of BRCA1 in breast cancer. Science 1995 Nov 3;270(5237):789-91.

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

4. Cortez D. et al: Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science. 1999 Nov 5;286(5442):1162-6.