Radiation-induced cell cycle arrest compromised by p21 deficiency

THE protein p21 is a dual inhibitor of cyclin-dependent kinases1á¤-3 and proliferating-cell nuclear antigen (PCNA)4, both of which are required for passage through the cell cycle. The p21 gene is under the transcriptional control of p53 (ref. 5), suggesting that p21 might promote p53-dependent cell cycle arrest or apoptosis. p21 has also been implicated in cell senescence6 and in cell-cycle withdrawal upon terminal differentiation7á¤-9. Here we investigate the role of p21 in these processes using chimaeric mice composed partly of p21 -/- and partly of p21 +/+ cells. Immunohistochemical studies of the p21 +/+ and p21 -/- components of adult small intestine indicated that deletion of p21 had no detectable effect on the migration-associated differentiation of the four principal intestinal epithelial cell lineages or on p53-dependent apoptosis following irradiation. However, p21 -/- mouse embryo fibroblasts are impaired in their ability to undergo Gl arrest following DNA damage.

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