The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair

Abstract

Homologous recombinational repair (HRR) of DNA damage is critical for maintaining genome stability and tumor suppression. RAD51 and BRCA2 colocalization in nuclear foci is a hallmark of HRR. BRCA2 has important roles in RAD51 focus formation and HRR of DNA double-strand breaks (DSBs). We previously reported that BCCIPα interacts with BRCA2. We show that a second isoform, BCCIPβ, also interacts with BRCA2 and that this interaction occurs in a region shared by BCCIPα and BCCIPβ. We further show that chromatin-bound BRCA2 colocalizes with BCCIP nuclear foci and that most radiation-induced RAD51 foci colocalize with BCCIP. Reducing BCCIPα by 90% or BCCIPβ by 50% by RNA interference markedly reduces RAD51 and BRCA2 foci and reduces HRR of DSBs by 20- to 100-fold. Similarly, reducing BRCA2 by 50% reduces RAD51 and BCCIP foci. These data indicate that BCCIP is critical for BRCA2- and RAD51-dependent responses to DNA damage and HRR.

ACKNOWLEDGMENTS

This research was supported by National Institute of Health NIEHS grant ES08353 and by U.S. Army Medical Research and Materiel Command grants DAMD17-02-1-0515 and DAMD17-03-1-0317 to Z.S., a U.S. Army Medical Research and Materiel Command postdoctoral fellowship (W81XWH-04-1-0566) to H.L., and grant CA77693 from the National Cancer Institute to J.A.N.