title: Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1.
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.
authors.affiliation: Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 78245, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: H
authors.initials: H
authors.lastname: Pan
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Flesken-Nikitin
authors.forename: P L
authors.initials: PL
authors.lastname: Chen
authors.forename: T G
authors.initials: TG
authors.lastname: Boyer
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019313:BRCA1 Protein / Q000172:deficiency / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004249:DNA Damage; D004268:DNA-Binding Proteins; D019398:Genes, BRCA1; D016158:Genes, p53; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D016335:Zinc Fingers; D000097642:GADD45 Proteins
chemical_list: D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000097642:GADD45 Proteins; C422407:ZNF350 protein, human