CONTINUOUS CYCLIN-E EXPRESSION INHIBITS PROGRESSION THROUGH ENDOREDUPLICATION CYCLES IN DROSOPHILA

Entry into S phase of the mitotic cell cycle is normally strictly depe ndent on progression through the preceding M phase. In contrast, durin g endoreduplication, which accompanies post-mitotic cell growth in man y organisms, repeated S phases occur without intervening M phases. Upo n transition from mitotic to endoreduplication cycles in Drosophila em bryos, expression of the mitotic cyclins A, B and B3 is terminated and Cyclin E expression is changed from a continuous into a periodic mode [1-3]. Here, we address whether these changes in cyclin expression ar e required for endoreduplication by continuously expressing Cyclin A, B, B3 or E in the salivary glands of Drosophila throughout late embryo nic and larval development. With the exception of Cyclin A, expression of which inhibited endoreduplication effectively but only in a few, a pparently randomly distributed, cells of the salivary gland, mitotic c yclin expression was found to have no effect. In contrast, Cyclin E ex pression resulted in a striking inhibition of endoreduplication and gr owth, preceded initially by an ectopic S phase occurring just after th e onset of ectopic Cyclin E expression. This observation is consistent with our previous findings that Cyclin E is required, and pulses of e ctopic expression are sufficient, for triggering endoreduplication Ii phases [4]. Our results indicate that Cyclin E activity, which trigger s DNA replication, needs to be down-regulated to allow a subsequent S phase in vivo. (C) Current Biology Ltd.