 Loss of Cdt2 expression increases p21 expression in cells and stabilizes p21 following UV-irradiation.CUL4A deletion results in delayed S phase entry in mouse embryonic fibroblasts, which is rescued by deletion of p21.In human retinal pigment epithelial cells, loss of Cdt2 expression also result in p21 dependent delayed S-phase entry, and re-expression of p21 in S-phase, which results cycles of incomplete replication, long term accumulation of p21, and in some cases induction of apoptosis.