ROLE OF BRCA1 IN RADIATION-INDUCED CENTROSOMAL CHECKPOINT

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IONIZING RADIATION 'HAS BEEN KNOWN TO INDUCED DNA DOUBLE STRAND BREAKS, WHICH RESULT IN ACTIVATION OF ATM. ACTIVATED ATM PHOSPHORYLATES VARIOUS PROTEINS INCLUDING BRCA1. BRCA1 HAS BEEN FOUND TO BE INVOLVED IN INHERITED MAMMARY CARCINOMA, AND IT IS THOUGHT TO HAVE A FUNCTION IN REPAIR OF DNA DOUBLE STRAND BREAKS. HERE, WE SHOW THAT BRCA1 COLOCALIZE WITH CENTROSOMAS. WITHOUT BRCA1 CENTROSOMES TEND TO OVERAMPLIFY, WHICH LEAD TO MULTIPOLAR DIVISION. FURTHERMORE, WE FOUND THAT ACTIVATED FORMS OF ATM, PHOSPHORYLATED ATM AT SERINE1981, ALSO COLOCALIZED WITH CENTROSOMES, WHICH INDICATE THAT ACTIVATED ATM CONSTITUTIVELY PHOSPHORYLATE BRCA1. THESE RESULTS INDICATE THAT ATM-MEDIATED PHOSPHORYLATION OF BRCA1 MAY REGULATE CENTROSOMAL DUPLICATION NOT ONLY IN _UNIRRADIATED CELLS BUT ALSO AFTER IRRADIATION.