Influence of cyclin type and dose on mitotic entry and progression in the early Drosophila embryo.
Cyclins are key cell cycle regulators, yet few analyses test their role in timing the events that they regulate. We used RNA interference and real-time visualization in embryos to define the events regulated by each of the three mitotic cyclins of Drosophila melanogaster, CycA, CycB, and CycB3. Each individual and pairwise knockdown results in distinct mitotic phenotypes. For example, mitosis without metaphase occurs upon knockdown of CycA and CycB. To separate the role of cyclin levels from the influences of cyclin type, we knocked down two cyclins and reduced the gene dose of the one remaining cyclin. This reduction did not prolong interphase but instead interrupted mitotic progression. Mitotic prophase chromosomes formed, centrosomes divided, and nuclei exited mitosis without executing later events. This prompt but curtailed mitosis shows that accumulation of cyclin function does not directly time mitotic entry in these early embryonic cycles and that cyclin function can be sufficient for some mitotic events although inadequate for others.
McCleland
Mark L
ML
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Farrell
Jeffrey A
JA
O'Farrell
Patrick H
PH
D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D018628:Gene Dosage / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D010641:Phenotype; D034622:RNA Interference / Q000502:physiology
C503695:Ccnb3 protein, mouse; D019925:Cyclin A; D019926:Cyclin B; D016213:Cyclins; D029721:Drosophila Proteins; C539905:cyclin B3, Drosophila; D016203:CDC2 Protein Kinase