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

Mol Cell. 2000 Oct;6(4):757-68. doi: 10.1016/s1097-2765(00)00075-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • BRCA1 Protein / deficiency
  • BRCA1 Protein / metabolism*
  • Base Sequence
  • Binding Sites
  • Cells, Cultured
  • DNA Damage
  • DNA-Binding Proteins*
  • Genes, BRCA1
  • Genes, p53
  • Intracellular Signaling Peptides and Proteins
  • Introns
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Proteins / genetics
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription Factors*
  • Zinc Fingers

Substances

  • BRCA1 Protein
  • DNA-Binding Proteins
  • GADD45 protein
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Repressor Proteins
  • Transcription Factors
  • ZNF350 protein, human

Associated data

  • GENBANK/AF295096