title: Mutations in mákos, a Drosophila gene encoding the Cdc27 subunit of the anaphase promoting complex, enhance centrosomal defects in polo and are suppressed by mutations in twins/aar, which encodes a regulatory subunit of PP2A.
abstract: The gene mákos (mks) encodes the Drosophila counterpart of the Cdc27 subunit of the anaphase promoting complex (APC/C). Neuroblasts from third-larval-instar mks mutants arrest mitosis in a metaphase-like state but show some separation of sister chromatids. In contrast to metaphase-checkpoint-arrested cells, such mutant neuroblasts contain elevated levels not only of cyclin B but also of cyclin A. Mutations in mks enhance the reduced ability of hypomorphic polo mutant alleles to recruit and/or maintain the centrosomal antigens gamma-tubulin and CP190 at the spindle poles. Absence of the MPM2 epitope from the spindle poles in such double mutants suggests Polo kinase is not fully activated at this location. Thus, it appears that spindle pole functions of Polo kinase require the degradation of early mitotic targets of the APC/C, such as cyclin A, or other specific proteins. The metaphase-like arrest of mks mutants cannot be overcome by mutations in the spindle integrity checkpoint gene bub1, confirming this surveillance pathway has to operate through the APC/C. However, mutations in the twins/aar gene, which encodes the 55kDa regulatory subunit of PP2A, do suppress the mks metaphase arrest and so permit an alternative means of initiating anaphase. Thus the APC/C might normally be required to inactivate wild-type twins/aar gene product.
authors.affiliation: Cancer Research UK, Cell Cycle Genetics Research Group, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Deak
authors.forename: Mary
authors.initials: M
authors.lastname: Donaldson
authors.forename: David M
authors.initials: DM
authors.lastname: Glover
mesh_terms: D000705:Anaphase / Q000502:physiology; D000818:Animals; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D002842:Chromatids / Q000235:genetics / Q000502:physiology; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D008938:Mitosis / Q000235:genetics; D009154:Mutation / Q000502:physiology; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000502:physiology; D014404:Tubulin / Q000378:metabolism
chemical_list: D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; C107964:CP190 protein, Drosophila; C577365:Cdc27 protein, Drosophila; D018797:Cell Cycle Proteins; C503698:CycB protein, Drosophila; D019925:Cyclin A; D019926:Cyclin B; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D014404:Tubulin; C072004:polo protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; C079898:tws protein, Drosophila