Yp. Tsao et al., THE INVOLVEMENT OF ACTIVE DNA-SYNTHESIS IN CAMPTOTHECIN-INDUCED G2 ARREST - ALTERED REGULATION OF P34CDC2 CYCLIN-B, Cancer research, 52(7), 1992, pp. 1823-1829
Cell cycle arrest in G2 phase is a common response to a variety of DNA
-damaging agents. The coupling between DNA damage and G2 arrest was st
udied in synchronized HeLa cells using camptothecin, a highly specific
inhibitor of topoisomerase I that damages DNA through the formation o
f reversible topoisomerase I-DNA cleavable complexes. Brief camptothec
in treatment of early S-phase HeLa cells caused arrest at G2 phase and
abolished the activation of p34cdc2 protein kinase. Both tyrosine dep
hosphorylation of p34cdc2 and cyclin B accumulation were altered. Thes
e cell cycle-dependent changes were not observed when DNA replication
was inhibited by aphidicolin during the brief camptothecin treatment.
Our results suggest that to produce G2 arrest, active DNA synthesis is
required at the time of camptothecin treatment, as was previously sho
wn for camptothecin-induced cytotoxicity. Furthermore, our results sug
gest that the interaction of the replication fork with DNA damage may
ultimately trigger altered regulation of p34cdc2/cyclin B, leading to
cell cycle arrest at the G2 phase.