The BARD1-CstF-50 interaction links mRNA 3 ' end formation to DNA damage and tumor suppression

The mRNA polyadenylation factor CstF interacts with the BRCA1-associated pr otein BARD1, and this interaction represses the nuclear mRNA polyadenylatio n machinery in vitro. Given the suspected role of BRCA1/BARD1 in DNA repair , we tested whether inhibition of mRNA processing is linked to DNA damage. Strikingly, we found that 3' cleavage in extracts from cells treated with h ydroxyurea or ultraviolet light was strongly, but transiently, inhibited. A lthough no changes were detected in CstF, BARD1, and BRCA1 protein levels, increased amounts of a CstF/BARD1/BRCA1 complex were detected. Supporting t he physiological significance of these results, a previously identified tum or-associated germline mutation in BARD1 (Gln564His) reduced binding to Cst F and abrogated inhibition of polyadenylation. Together these results indic ate a link between mRNA 3' processing and DNA repair and tumor suppression.