Radiation-induced cell cycle arrest compromised by p21 deficiency

THE protein p21 is a dual inhibitor of cyclin-dependent kinases^1-3 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 differentiation^7-9. 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.