Continuous Cyclin E expression inhibits progression through endoreduplication cycles in Drosophila

Abstract

Entry into S phase of the mitotic cell cycle is normally strictly dependent on progression through the preceding M phase. In contrast, during endoreduplication, which accompanies post-mitotic cell growth in many organisms, repeated S phases occur without intervening M phases. Upon transition from mitotic to endoreduplication cycles in Drosophila embryos, 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 are required for endoreduplication by continuously expressing Cyclin A, B, B3 or E in the salivary glands of Drosophila throughout late embryonic and larval development. With the exception of Cyclin A, expression of which inhibited endoreduplication effectively but only in a few, apparently randomly distributed, cells of the salivary gland, mitotic cyclin expression was found to have no effect. In contrast, Cyclin E expression resulted in a striking inhibition of endoreduplication and growth, preceded initially by an ectopic S phase occurring just after the onset of ectopic Cyclin E expression. This observation is consistent with our previous findings that Cyclin E is required, and pulses of ectopic expression are sufficient, for triggering endoreduplication S phases [4]. Our results indicate that Cyclin E activity, which triggers DNA replication, needs to be down-regulated to allow a subsequent S phase in vivo.

Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

“…One example are the polytene salivary gland cells of D. melanogaster. Also in this case, cell size is correlated with ploidy, and salivary gland cells remain smaller when endoreplication is inhibited (Follette et al, 1998;Weiss et al, 1998). Here we show that ubc9.1 morphant cells with a DNA content of 8n are larger in size than 2n and 4n cells (Figure 8, G-I), suggesting a similar direct correlation between cell size and ploidy.…”

Cyclin E in normal and neoplastic cell cycles

“…In fact, the trophoblastic failure caused early embryonic lethality, and cyclin E-null animals were only obtained after tetraploid complementation rescue. Previous studies in flies suggested an intimate relationship between cyclin E expression, MCM proteins and endoreduplication (Follette et al, 1998;Su and O'Farrell, 1998;Weiss et al, 1998), and cyclin E deregulation has been linked to megakaryopoiesis in mammals as well (Garcia et al, 2000). The knockout mice extend these observations, and show that cyclin E is required for endocycles, and this probably involves defective MCM loading.…”

Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles

“…Drosophila and mouse trophoblasts, in which both cyclins A and B are no longer expressed, cyclin E appears to cycle as it does in mitotic cycles (Follette et al, 1998;Sauer et al, 1995). Moreover, continuous expression inhibits rereplication in Drosophila embryos (Follette et al, 1998;Weiss et al, 1998). Our results show that at least the establishment of an extra cycle can occur in the presence of cyclin E and that in fact the accumulation of cyclin E in cells in late S and G2 phases appears to directly relate to the ability to establish a re-replication cycle.…”