Dissociation of BRCA1s DNA Repair and Checkpoint Functions from DNA Damage-Induced CytotoxicityA Dep

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  Dr.Recent reports have revealed the tumor suppressor B RCA 1 to be a nuclear shuttling protein, and several hereditary mutations are known to cause aberrant localization of B RCA1.This suggests that BRCA1 subcellular localization may be important in the etiology of cancer development, progression, and response to therapy.Here we report nuclear accumulation of wild type BRCA1 in sporadic breast cancer when p53 is dysfunctional.Importantly, we demonstrate that the effect of BRCA1 on radiosensitivity is primarily determined by p53-mediated regulation of BRCA1 subcellular localization.
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