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Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes.

The BRCA1 gene product and its stoichiometric binding partner, BARD1, play a vital role in the cellular response to DNA damage. However, how they acquire specific biochemical functions after DNA damage is poorly understood. Following exposure to genotoxic stress, DNA damage-specific interactions were observed between BRCA1/BARD1 and the DNA damage-response proteins, TopBP1 and Mre11/Rad50/NBS1. Two distinct DNA damage-dependent super complexes emerged; their activation was dependent, in part, on the actions of specific checkpoint kinases, and each super complex contributed to a distinctive aspect of the DNA damage response. The results support a new, multifactorial model that describes how genotoxic stress enables BRCA1 to execute a diverse set of DNA damage-response functions.

Pubmed ID: 16391231

Authors

  • Greenberg RA
  • Sobhian B
  • Pathania S
  • Cantor SB
  • Nakatani Y
  • Livingston DM

Journal

Genes & development

Publication Data

January 1, 2006

Associated Grants

None

Mesh Terms

  • BRCA1 Protein
  • Carrier Proteins
  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • DNA Damage
  • DNA Repair
  • DNA Repair Enzymes
  • DNA-Binding Proteins
  • Humans
  • Nuclear Proteins
  • Protein Binding
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases