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.