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) cycl in-dependent kinases (Cdks) in vitro and is transcriptionally regulate d by wild-type p53. In addition, p21(Sdi1) has been found to inhibit D NA replication by direct interaction with proliferating cell nuclear a ntigen. In this study we analyzed normal human fibroblast cells arrest ed in G(0) and determined that an excess of p21(Sdi1) was present afte r immunodepletion of various cyclins and Cdks, in contrast to mitogen- stimulated cells in early S phase. Expression of antisense p21(Sdi1) R NA in G(0)-arrested cells resulted in induction of DNA synthesis as we ll as entry into mitosis. These results suggest that p21(Sdi1) functio ns in G(0) and early G(1) and that decreased expression of the gene is necessary for cell cycle progression.