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- Title
Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer.
- Authors
Clapperton, Julie A; Manke, Isaac A; Lowery, Drew M; Ho, Timmy; Haire, Lesley F; Yaffe, Michael B; Smerdon, Stephen J
- Abstract
Germline mutations in the BRCA1 tumor suppressor gene often result in a significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. We report the X-ray crystal structure at a resolution of 1.85 A of the BRCA1 tandem BRCT domains in complex with a phosphorylated peptide representing the minimal interacting region of the DEAH-box helicase BACH1. The structure reveals the determinants of this novel class of BRCA1 binding events. We show that a subset of disease-linked mutations act through specific disruption of phospho-dependent BRCA1 interactions rather than through gross structural perturbation of the tandem BRCT domains.
- Publication
Nature structural & molecular biology, 2004, Vol 11, Issue 6, p512
- ISSN
1545-9993
- Publication type
Journal Article
- DOI
10.1038/nsmb775