Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response

Science. 2007 May 25;316(5828):1202-5. doi: 10.1126/science.1139621.

Abstract

Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of breast and ovarian cancers. BRCA1 participates in the cellular DNA damage response. We report the identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 contains a tandem ubiquitin-interacting motif domain, which is required for its binding with ubiquitin in vitro and its damage-induced foci formation in vivo. Moreover, RAP80 specifically recruits BRCA1 to DNA damage sites and functions with BRCA1 in G2/M checkpoint control. Together, these results suggest the existence of a ubiquitination-dependent signaling pathway involved in the DNA damage response.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • BRCA1 Protein / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Cycle
  • Cell Line, Tumor
  • DNA / metabolism*
  • DNA / radiation effects
  • DNA Damage*
  • DNA Repair / physiology*
  • DNA-Binding Proteins
  • HeLa Cells
  • Histone Chaperones
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Small Interfering
  • Radiation, Ionizing
  • Ubiquitin / metabolism*

Substances

  • BRCA1 Protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • Histone Chaperones
  • Nuclear Proteins
  • RNA, Small Interfering
  • UIMC1 protein, human
  • Ubiquitin
  • DNA