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.
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
Genes Dev.
Date: Jan. 01, 2006
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