Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-06

AUTHORS

T Waldman, C Lengauer, K W Kinzler, B Vogelstein

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. More... »

PAGES

713-716

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/381713a0

DOI

http://dx.doi.org/10.1038/381713a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028535114

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8649519


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