Flies without a spindle checkpoint.
Mad2 has a key role in the spindle-assembly checkpoint (SAC) - the mechanism delaying anaphase onset until all chromosomes correctly attach to the spindle. Here, we show that unlike every other reported case of SAC inactivation in metazoans, mad2-null Drosophila are viable and fertile, and their cells almost always divide correctly despite having no SAC and an accelerated 'clock', which is caused by premature degradation of cyclin B. Mitosis in Drosophila does not need the SAC because correct chromosome attachment is achieved very rapidly, before even the cell lacking Mad2 can initiate anaphase. Experimentally reducing spindle-assembly efficiency renders the cells Mad2-dependent. In fact, the robustness of the SAC may generally mask minor mitotic defects of mutations affecting spindle function. The reported lethality of other Drosophila SAC mutations may be explained by their multifunctionality, and thus the 'checkpoint' phenotypes previously ascribed to these mutations should be considered the consequence of eliminating both the checkpoint and a second mitotic function.
Buffin
Eulalie
E
CNRS, Centre de Génétique Moléculaire, Ave de la Terrasse, 91198 Gif sur Yvette, France.
Emre
Doruk
D
Karess
Roger E
RE
D000705:Anaphase / Q000502:physiology; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D003078:Colchicine / Q000494:pharmacology; D019926:Cyclin B / Q000378:metabolism; D004330:Drosophila / Q000187:drug effects / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D007814:Larva / Q000502:physiology; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D009154:Mutation; D010641:Phenotype; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
D018797:Cell Cycle Proteins; C503698:CycB protein, Drosophila; D019926:Cyclin B; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins; D050257:Tubulin Modulators; C106174:asp protein, Drosophila; C098130:cnn protein, Drosophila; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D003078:Colchicine