RADIATION-INDUCED CELL-CYCLE ARREST COMPROMISED BY P21 DEFICIENCY

THE protein p21 is a dual inhibitor of cyclin-dependent kinases(1-3) a nd proliferating-cell nuclear antigen (PCNA)(4), both of which are req uired for passage through the cell cycle. The p21 gene is under the tr anscriptional control of p53 (ref. 5), suggesting that p21 might promo te p53-dependent cell cycle arrest or apoptosis. p21 has also been imp licated in cell senescence(6) and in cell-cycle withdrawal upon termin ation differentiation(7-9). Here we investigate the role of p21 in the se processes using chimaeric mice composed partly of p21(-/-) and part ly of p21(+/+) cells. Immunohistochemical studies of the p21(+/+) and p21(-/-) components of adult small intestine indicated that deletion o f p21 had no detectable effect on the migration-associated differentia tion of the four principal intestinal epithelial cell lineages or on p 53-dependent apoptosis following irradiation. However, p21(-/-) mouse embryo fibroblasts are impaired in their ability to undergo G1 arrest following DNA damage.