Identification of BRCA1-IRIS, a BRCA1 locus product

Nat Cell Biol. 2004 Oct;6(10):954-67. doi: 10.1038/ncb1171. Epub 2004 Sep 26.


Breast cancer is the most common malignancy among women, and mutations in the BRCA genes produce increased susceptibility to these malignancies in certain families. Here we identify BRCA1-IRIS as a 1,399-amino-acid BRCA1 gene product encoded by an uninterrupted open reading frame that extends from codon 1 of the known BRCA1 open reading frame to a termination point 34 triplets into intron 11. Unlike full-length BRCA1 (p220), BRCA1-IRIS is exclusively chromatin-associated, fails to interact with BARD1 in vivo or in vitro and exhibits unique nuclear immunostaining. Unlike BRCA1FL (or p220), BRCA1-IRIS also co-immunoprecipitated with DNA-replication-licensing proteins and with known replication initiation sites. Suppression of BRCA1-IRIS expression hindered the normal departure of geminin from pre-replication complexes, and depressed the rate of cellular DNA replication and possibly initiation-related synthesis. In contrast, BRCA1-IRIS overexpression stimulated DNA replication. These data imply that endogenous BRCA1-IRIS positively influences the DNA replication initiation machinery.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / metabolism
  • BRCA1 Protein / chemistry*
  • BRCA1 Protein / isolation & purification
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / isolation & purification
  • Codon
  • Conserved Sequence
  • DNA Replication*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epitopes
  • Exons
  • Female
  • Gene Deletion
  • Genes, BRCA1*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Open Reading Frames
  • Precipitin Tests
  • RNA, Messenger / biosynthesis
  • Sequence Homology, Amino Acid


  • Antibodies, Monoclonal
  • BRCA1 Protein
  • BRCA1 protein, human
  • Chromosomal Proteins, Non-Histone
  • Codon
  • Epitopes
  • RNA, Messenger