EXIT FROM G(0) AND ENTRY INTO THE CELL-CYCLE OF CELLS EXPRESSING P21(SDI1) ANTISENSE RNA

p21(Sdi1) (also known as Cip1 and Waf1), an inhibitor of DNA synthesis cloned from senescent human fibroblasts, is an inhibitor of G(1) cyclin-dependent kinases (Cdks) in vitro and is transcriptionally regulated by wild-type p53. In addition, p21(Sdi1) has been found to inhibit DNA replication by direct interaction with proliferating cell nuclear antigen. In this study we analyzed normal human fibroblast cells arrested in G(0) and determined that an excess of p21(Sdi1) was present after immunodepletion of various cyclins and Cdks, in contrast to mitogen-stimulated cells in early S phase. Expression of antisense p21(Sdi1) RNA in G(0)-arrested cells resulted in induction of DNA synthesis as well as entry into mitosis. These results suggest that p21(Sdi1) functions in G(0) and early G(1) and that decreased expression of the gene is necessary for cell cycle progression.