ROLE OF BRCA1 IN RADIATION-INDUCED CENTROSOMAL CHECKPOINT

已知电离辐射可诱导DNA双链断裂，从而导致ATM的激活。激活的ATM可使包括BRCA1在内的各种蛋白质磷酸化。BRCA1已被发现与遗传性乳腺癌有关，并被认为在DNA双链断裂的修复中具有功能。在这里，我们展示了BRCA1与CENTROSOMAS的结合。没有BRCA1，中心体倾向于过度分裂，从而导致多极分裂。此外，我们还发现ATM的活化形式，在SERINE1981将ATM磷酸化，也与中心体共存，这表明激活的ATM对BRCA1具有结构性磷酸化作用。这些结果表明，ATM介导的BRCA1的磷酸化不仅可以调节未照射细胞的中心体复制，而且在照射后也可以调节中心体的复制。

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.