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

Lei Zheng, Hongyi Pan, Shang Li, Andrea Flesken-Nikitin, Phang Lang Chen, Thomas G. Boyer, Wen Hwa Lee

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)757-768
Number of pages12
JournalMolecular cell
Volume6
Issue number4
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1'. Together they form a unique fingerprint.

  • Cite this