Regulation of ATM/DNA-PKcs Phosphorylation by BRCA1-Associated BAAT1

BRCA1 has been implicated in the DNA damage pathway and regulation of genome stability, however, it does not contain intrinsic catalytic activity to repair the DNA lesions. Thus, a potential activity of BRCA1 is to assemble proteins that sense DNA damage and to transduce checkpoint signals to downstream. We have recently isolated a protein termed BAAT1, which binds to BRCA1, ATM, DNA-PKcs, and SMC1. Phosphorylation of ATM/DNA-PKcs is greatly reduced in BAAT1-knockdown cells, suggesting that sensing of DNA lesions mediated by BRCA1/BAAT1 is critical for activation of these kinases.