BRCA1

BRCA1 (breast and ovarian cancer susceptibility protein 1) is a RING finger protein containing a BRCT domain. BRCA1 exists as a heterodimer with 22 possible isoforms. The full length protein has a reported molecular weight of 208 kD. BRCA1 localizes to the mitotic spindle microtubules, centriole walls, pericentriolar fibers at centrosomes. Unphosphorylated BRCA1 localizes on chromosomes from metaphase through telophase; phosphorylated BRCA1 resides in inner chromosomal structure, centrosome, cleavage furrow during prophase through telophase, and relocalizes to the perinuclear region when cells are subjected to IR or UV radiation in S phase. BRCA1 acts as a tumor suppressor and can function as a secreted growth inhibitory protein, participate in transcription coupled repair of oxidative DNA damage, X-chromosome inactivation, and can function as a E3 ubiquitin ligase. BRCA1 can be transcriptionally downregulated by Ets-2, Brg-1, and Hmga-1. BRCA1 can be modified by glycosylation, ubiquitination and phosphorylation by CDK4, ATM/ATR, cdk2, and hChk2. The BRCA1 protein has been reported to interact with RNA polymerase II holoenzyme and BARD1. BRCA1 contains at least two nuclear localization signals and is proposed to be a tumor suppressor protein. It is a serine phosphoprotein that undergoes hyperphosphorylation during late G1 and S phases of the cell cycle and is transiently dephosphorylated early after M phase. BRCA1 protein alters in a qualitative and quantitative manner during cell cycle progression. The amount of BRCA1 protein is highest during S phase and remains elevated toward G2 / M, before it declines in early G1 phase. Inherited loss of BRCA1 function confers an increased susceptibility for both breast and ovarian cancer.