Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1.
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.
Mesh Terms:
Amino Acid Sequence, Animals, BRCA1 Protein, 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, Repressor Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Transcription Factors, Zinc Fingers
Amino Acid Sequence, Animals, BRCA1 Protein, 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, Repressor Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Transcription Factors, Zinc Fingers
Mol. Cell
Date: Oct. 01, 2000
PubMed ID: 11090615
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