Sequence-specific transcriptional corepressor function for BRCA1 through anovel zinc finger protein, ZBRK1

BRCA1 has been implicated in the transcriptional regulation of DNA damage-i nducible genes that function in cell cycle arrest. To explore the mechanist ic basis for this regulation, a novel human gene, ZBRK1, which encodes a 60 kDa protein with an N-terminal KRAB domain and eight central zinc fingers, was identified by virtue of its interaction with BRCA1 in vitro and in viv o. ZBRK1 binds to a specific sequence, GGGxxx CAGxxxTTT, within GADD45 intr on 3 that supports the assembly of a nuclear complex minimally containing b oth ZBRK1 and BRCA1. ZBRK1 represses transcription through this recognition sequence in a BRCA1-dependent manner. These results thus reveal a novel co repressor function for BRCA1 and provide a mechanistic basis for the biolog ical activity of BRCA1 through sequence-specific transcriptional regulation .