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Ataxia Telangiectasia-related Protein Is Involved in the Phosphorylation of BRCA1 following Deoxyribonucleic Acid Damage¹

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota 55905

The breast/ovarian cancer susceptibility gene BRCA1 exerts its tumor suppressor function, at least in part, by participating in DNA repair and/or DNA damage-responsive pathways. BRCA1 protein is hyperphosphorylated following various DNA-damaging events. Here, we report that the ataxia telangiectasia mutated protein-related protein kinase (ATR) is involved in the phosphorylation of BRCA1 following gamma radiation and hydroxyurea treatment. We have shown that ATR can phosphorylate several BRCA1 fragments in vitro and that a kinase-inactive mutant of ATR interacts with BRCA1 in vivo. Taken together, these results suggest that ATR directly phosphorylates BRCA1 following DNA damage.

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