Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer

Nat Struct Mol Biol. 2004 Jun;11(6):512-8. doi: 10.1038/nsmb775. Epub 2004 May 9.


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 types

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

MeSH terms

  • BRCA1 Protein / chemistry
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • Basic-Leucine Zipper Transcription Factors
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Nucleus / chemistry
  • Crystallography, X-Ray
  • Fanconi Anemia Complementation Group Proteins
  • Female
  • Humans
  • Microscopy, Fluorescence
  • Mutation
  • Nuclear Proteins / metabolism
  • Phosphopeptides / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Transcription Factors / metabolism*
  • Transfection


  • BACH1 protein, human
  • BRCA1 Protein
  • Basic-Leucine Zipper Transcription Factors
  • Fanconi Anemia Complementation Group Proteins
  • Nuclear Proteins
  • Phosphopeptides
  • Transcription Factors

Associated data

  • PDB/1T15