DNA REREPLICATION IN THE PRESENCE OF MITOTIC SPINDLE INHIBITORS IN HUMAN AND MOUSE FIBROBLASTS LACKING EITHER P53 OR PRB FUNCTION

Cell cycle checkpoints are biochemical signal transduction pathways th at prevent downstream events from being initiated until upstream proce sses are completed, We analyzed whether the p53 or pRb tumor suppresso rs are involved in a checkpoint(s) that prevents DNA rereplication in the presence of drugs that interfere with spindle assembly, Normal mou se and human fibroblasts arrested with a 4N DNA content when treated w ith nocodazole and Colcemid, whereas isogeneic p53-deficient or pRb-de ficient derivatives became polyploid, Flow cytometric and cytogenetic analyses demonstrated that the polyploidy resulted from genome-wide re replication without an intervening mitosis, Thus, p53 and pRb help mai ntain normal cell ploidy by preventing DNA rereplication prior to mito tic division.