title: DNA rereplication in the presence of mitotic spindle inhibitors in human and mouse fibroblasts lacking either p53 or pRb function.
abstract: Cell cycle checkpoints are biochemical signal transduction pathways that prevent downstream events from being initiated until upstream processes are completed. We analyzed whether the p53 or pRb tumor suppressors are involved in a checkpoint(s) that prevents DNA rereplication in the presence of drugs that interfere with spindle assembly. Normal mouse and human fibroblasts arrested with a 4N DNA content when treated with nocodazole and Colcemid, whereas isogeneic p53-deficient or pRb-deficient derivatives became polyploid. Flow cytometric and cytogenetic analyses demonstrated that the polyploidy resulted from genome-wide rereplication without an intervening mitosis. Thus, p53 and pRb help maintain normal cell ploidy by preventing DNA rereplication prior to mitotic division.
authors.affiliation: Department of Cell and Developmental Biology A. Monroy, University of Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Leonardo
authors.forename: S H
authors.initials: SH
authors.lastname: Khan
authors.forename: S P
authors.initials: SP
authors.lastname: Linke
authors.forename: V
authors.initials: V
authors.lastname: Greco
authors.forename: G
authors.initials: G
authors.lastname: Seidita
authors.forename: G M
authors.initials: GM
authors.lastname: Wahl
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D003703:Demecolcine / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects*; D005434:Flow Cytometry; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006801:Humans; D051379:Mice; D015739:Nocodazole / Q000494:pharmacology*; D011003:Ploidies; D016160:Retinoblastoma Protein / Q000172:deficiency*; D015398:Signal Transduction / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*
chemical_list: D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D015739:Nocodazole; D003703:Demecolcine