Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21 - PubMed (original) (raw)
. 1996 Jun 20;381(6584):713-6.
doi: 10.1038/381713a0.
Affiliations
- PMID: 8649519
- DOI: 10.1038/381713a0
Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21
T Waldman et al. Nature. 1996.
Abstract
Precise coordination of the S and M phases of the eukaryotic cell cycle is critical not only for normal cell division, but also for effective growth arrest under conditions of stress. When damaged, a cell must communicate signals to both the mitotic and DNA synthesis machineries so that a mitotic block is not followed by an extra S phase, or vice versa. The biochemical mechanisms regulating this coordination, termed checkpoints, have been identified in lower eukaryotes, but are largely unknown in mammalian cells. Here we show that p21 WAF1/CIP1, the prototype inhibitor of cyclin-dependent kinases (CDKs), is required for this coordination in human cells. In the absence of p21, DNA-damaged cells arrest in a G2-like state, but then undergo additional S phases without intervening normal mitoses. They thereby acquire grossly deformed, polyploid nuclei and subsequently die through apoptosis. Perhaps not by coincidence, the DNA-damaging agents that can cause S/M uncoupling are used in the clinic to kill cancer cells preferentially.
Comment in
- Cell-cycle control and its watchman.
Jacks T, Weinberg RA. Jacks T, et al. Nature. 1996 Jun 20;381(6584):643-4. doi: 10.1038/381643a0. Nature. 1996. PMID: 8649505 No abstract available. - p53 and treatment of bladder cancer.
Cote RJ, Esrig D, Groshen S, Jones PA, Skinner DG. Cote RJ, et al. Nature. 1997 Jan 9;385(6612):123-5. doi: 10.1038/385123b0. Nature. 1997. PMID: 8990112 Clinical Trial. No abstract available.
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