BACH1 is a DNA repair protein supporting BRCA1 damage response

Abstract

The link between defects in BRCA1 and breast cancer development may be best understood by deciphering the role of associated proteins. BRCA1 associated C-terminal helicase (BACH1) interacts directly with the BRCA1 C-terminal BRCT repeats, which are important for BRCA1 DNA repair and are mutated in the majority of BRCA1 familial cancers. Thus, BACH1 is a likely candidate for mediating BRCA1 DNA repair and tumor suppression functions. Although previous evidence using overexpression of a dominant negative BACH1 has suggested that BACH1 is involved in BRCA1-DNA repair function, our results using BACH1 deficient cells provide direct evidence for involvement of BACH1 in DNA repair as well as for localizing BRCA1. Following DNA damage BACH1 is modified by phosphorylation, displays a BRCA1-like nuclear foci pattern and colocalizes with gamma-H2AX. Given that the BACH1/BRCA1 complex is unaltered by DNA damage and the intensity of BRCA1 foci is diminished in BACH1 deficient cells, BACH1 may serve to not only facilitate DNA repair, but also maintain BRCA1 in DNA damage foci.