BRCA1 phosphorylation: biological consequences.

More than a decade has passed since BRCA1, breast cancer tumor suppressor 1, was isolated by reverse genetics in 1994. Its molecular structure and potential function have been extensively studied; both mouse genetics and a cell culture system revealed that BRCA1 is a 220,240 kD nuclear phosphoprotein, it regulates transcription, its loss leads to genome instability and in turn, cell transformation. Significantly, DNA checkpoint associated kinases have been shown to phosphorylate specific residues of BRCA1 under conditions of DNA damage, making cells sensitive or resistant to various stresses. Our recent findings support the notion that UV induced phosphorylation of particular residues of the protein is crucial for activation of caspase 3. This article will focus on the BRCA1 kinases, the identification of the phosphorylation residues, and the biological consequences of BRCA1's phosphorylation for regulation of cell proliferation.