Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes
AuthorsGreenberg, Roger A.
Cantor, Sharon B.
Livingston, David M.
UMass Chan AffiliationsDepartment of Cancer Biology
Cell Cycle Proteins
Cell Line, Tumor
DNA Repair Enzymes
Tumor Suppressor Proteins
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AbstractThe 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.
SourceGenes Dev. 2006 Jan 1;20(1):34-46. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/26305
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