Johnson N, Li YC, Walton ZE et al.
Dana Farber Cancer Institute, Boston, MA, USA.
Nat Med 2011;17:875–82.
Editor’s note: Inherited mutations in the BRCA1 and BRCA2 genes account for approximately 5–10% of breast cancers. Cells that have lost functional BRCA genes are deficient in homologous DNA recombination and this has been exploited in clinical trials of treatment of BRCA-positive breast cancer patients using poly(ADP-ribose) polymerase (PARP) inhibitors. When PARP is inhibited, single-stranded DNA breaks degenerate to the more lethal double-stranded breaks that require repair by homologous recombination. As cells lacking functional BRCA cannot carry out homologous recombination repair, these cells are highly susceptible to the action of PARP inhibitors. The current study demonstrates that CDK1, a component of the cell cycle machinery, phosphorylates BRCA1 and this phosphorylation is necessary for the formation of foci at sites of DNA damage and for BRCA1’s function in homologous recombination. This means that cancer cells that are deficient in CDK1 or in which CDK1 is inhibited are defective in DNA homologous recombination and so are sensitized to PARP inhibitors. This results in loss of CDK1 activity, endowing a state of BRCA-ness on cancer cells.