title: Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition.
abstract: The timing mechanism for mitotic progression is still poorly understood. The spindle assembly checkpoint (SAC), whose reversal upon chromosome alignment is thought to time anaphase [1-3], is functional during the rapid mitotic cycles of the Drosophila embryo; but its genetic inactivation had no consequence on the timing of the early mitoses. Mitotic cyclins-Cyclin A, Cyclin B, and Cyclin B3-influence mitotic progression and are degraded in a stereotyped sequence [4-11]. RNAi knockdown of Cyclins A and B resulted in a Cyclin B3-only mitosis in which anaphase initiated prior to chromosome alignment. Furthermore, in such a Cyclin B3-only mitosis, colchicine-induced SAC activation failed to block Cyclin B3 destruction, chromosome decondensation, or nuclear membrane re-assembly. Injection of Cyclin B proteins restored the ability of SAC to prevent Cyclin B3 destruction. Thus, SAC function depends on particular cyclin types. Changing Cyclin B3 levels showed that it accelerated progress to anaphase, even in the absence of SAC function. The impact of Cyclin B3 on anaphase initiation appeared to decline with developmental progress. Our results show that different cyclin types affect anaphase timing differently in the early embryonic divisions. The early-destroyed cyclins-Cyclins A and B-restrain anaphase-promoting complex/cyclosome (APC/C) function, whereas the late-destroyed cyclin, Cyclin B3, stimulates function. We propose that the destruction schedule of cyclin types guides mitotic exit by affecting both Cdk1 and APC/C, whose activities change as each cyclin type is lost.
authors.affiliation: Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94158-2517, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry, University of California, San Francisco, San Francisco, CA 94158-2517, USA. Electronic address: ofarrell@cgl.ucsf.edu.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: O'Farrell
mesh_terms: D000705:Anaphase / Q000235:genetics / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D019925:Cyclin A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D008297:Male; D008677:Metaphase / Q000235:genetics / Q000502:physiology; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological
chemical_list: C503698:CycB protein, Drosophila; D019925:Cyclin A; D019926:Cyclin B; D029721:Drosophila Proteins; C539905:cyclin B3, Drosophila