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Mol Cell. 2000 Oct;6(4):757-68.

Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1.

Author information

1
Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 78245, USA.

Abstract

BRCA1 has been implicated in the transcriptional regulation of DNA damage-inducible genes that function in cell cycle arrest. To explore the mechanistic 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 vivo. ZBRK1 binds to a specific sequence, GGGxxx CAGxxxTTT, within GADD45 intron 3 that supports the assembly of a nuclear complex minimally containing both ZBRK1 and BRCA1. ZBRK1 represses transcription through this recognition sequence in a BRCA1-dependent manner. These results thus reveal a novel corepressor function for BRCA1 and provide a mechanistic basis for the biological activity of BRCA1 through sequence-specific transcriptional regulation.

PMID:
11090615
DOI:
10.1016/s1097-2765(00)00075-7
[Indexed for MEDLINE]
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