Requirement of ATM-Dependent Phosphorylation of Brca1

[Rcjohnsen]

Cell Biology   

Requirement of ATM-Dependent Phosphorylation of Brca1 in the DNA Damage
Response to Double-Strand Breaks 

David Cortez, 1, 2  Yi Wang, 1, 3  Jun Qin, 1, 3  Stephen J. Elledge 1, 2, 4*  
The Brca1 (breast cancer gene 1) tumor suppressor protein is phosphorylated in
response to DNA damage. Results from this study indicate that the checkpoint
protein kinase ATM (mutated in ataxia telangiectasia) was required for
phosphorylation of Brca1 in response to ionizing radiation. ATM resides in a
complex with Brca1 and phosphorylated Brca1 in vivo and in vitro in a region
that contains clusters of serine-glutamine residues. Phosphorylation of this
domain appears to be functionally important because a mutated Brca1 protein
lacking two phosphorylation sites failed to rescue the radiation
hypersensitivity of a Brca1-deficient cell line. Thus, phosphorylation of Brca1
by the checkpoint kinase ATM may be critical for proper responses to DNA
double-strand breaks and may provide a molecular explanation for the role of
ATM in breast cancer

Article in Sci.286:1162-1166 1999 5 Nov
available in PDF on request
Roger.