The roles of Drosophila cyclins A and B in mitotic control

Abstract

SummaryWe have cloned, sequenced, and characterized the expression of a Drosophila cyclin B gene. The independent evolutionary conservation of A-and B-type cyclins implies that they have distinct roles. Indeed, in mutant embryos deficient in cyclin A, cells that accumulate only cyclin B do not enter mitosis. Thus, in vivo, cyclin B is not sufficient for mitosis. Furthermore, we find that the two cyclins are coexpressed in all proliferating cells throughout development. Though lacking a formal demonstration that cyclin B is essential as it is in other organisms, we propose that each of these proteins fulfills a distinct and essential role in the cell cycle.

Triggering the all-or-nothing switch into mitosis

“…However, a single B-type cyclin and Cdk1 can support a complete cell cycle in both the budding yeast Saccharomyces cerevisiae and in S. pombe 3,4 . In Drosophila, cyclin A:Cdk1 can drive either mitosis or S phase, depending on the status of the cell 5,6 . Thus, there is a mechanism that can define the outcome of cyclin:Cdk1 activation independent of cyclin:CDK specialization.…”

“…A Drosophila mutant lacking cyclin B is viable, albeit with a slightly disturbed mitosis 7 . Further genetic analysis has led to the demonstration that there are three distinct cyclins that make overlapping contributions to mitosis 5,7,8 . Cyclin A is the only cyclin that is essential for mitosis in Drosophila: cyclin A mutants arrest in G2, indicating that this cyclin has a role in triggering entry into mitosis 5,9 .…”

“…Further genetic analysis has led to the demonstration that there are three distinct cyclins that make overlapping contributions to mitosis 5,7,8 . Cyclin A is the only cyclin that is essential for mitosis in Drosophila: cyclin A mutants arrest in G2, indicating that this cyclin has a role in triggering entry into mitosis 5,9 . Cyclin B3 (which, despite its name, is not a subtle variant of cyclin B but a separate, more distantly related, cyclin type that is conserved from Caenorhabditis elegans to vertebrates 10,11 ) also has a mitotic role 7 .…”

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

“…One system in which re-replication has been more extensively studied is the fruit¯y Drosophila, in which speci®c subsets of cells respond to spatial and temporal controls to become polyploid during oogenesis and embryonic and larval development (Duronio and O'Farrell, 1994;Edgar, 1995;Smith and Orr-Weaver, 1991). Genetic analyses have proved that cyclin E is directly implicated in the establishment of Drosophila endocycles (Duronio and O'Farrell, 1995;Knoblich et al, 1994;Lilly and Spradling, 1996;Richardson et al, 1993;Sauer et al, 1995), and that these can occur in the absence of mitotic cyclins A and B, cdc2 or string (Drosophila cdc25C), the phosphatase that ultimately activates the cyclin B-cdc2 at the G2/M transition (Lehner and O'Farrell, 1990;Smith and Orr-Weaver, 1991;Stern et al, 1993). Also, in mouse trophoblasts, cyclin E appears to be expressed during polyploidization, whereas expression of cyclins A and B, and cdc2 is abolished (MacAuley et al, 1998).…”

In vitro fusion of endocytic vesicles is inhibited by cyclin A-cdc2 kinase.

“…Although both cyclin A and cyclin B are required for the mitotic cycle Lehner and O'Farrell, 1990;Pagano et al, 1992), the precise role that each cyclin plays in mitosis-specific events has yet to be determined. Cyclin A and B accumulate during the cell cycle (Evans et al, 1983;Hunter, 1989, 1991), and either cyclin mRNA can promote maturation when microinjected into stage VI Xenopus oocytes (Swenson et al, 1986;Pines and Hunt, 1987) as can either cyclin protein (Roy et al, 1991).…”