CYCLIN DEPENDENT KINASES W/ IRRADIATION INDUCED G1/S &LATE S PHASE CHECKPOINTS

$7,662P41FY2000RRNIH

University Of Calif-Los Alamos Nat Lab, Los Alamos NM

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Abstract

We investigated the time dependent effects of 8 Gy of gamma radiation on cyclin-dependent kinases (Cdks) and incorporation of BrdU through the S phase of Chinese hamster ovary (CHO) cells. Results obtained indicated that the transient G1-phase delay or G1/S phase check point is mediated by inhibition of cyclin E-Cdk2 and point to the existence of a radiation induced S phase checkpoint located about 75% into S phase involving the inhibition of cyclin A-Cdk2 by a p53/Waf1-independent pathway in CHO cells. Currently we are also investigating the role of cell cycle regulatory proteins, cyclin D1 and p27, in DNA damage check point regulation. Levels of these proteins have been found to be reduced in irradiated normal, human cells.

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