Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage.
In yeast, anaphase entry depends on Pds1 proteolysis, while chromosome re-duplication in the subsequent S-phase involves degradation of mitotic cyclins such as Clb2. Sequential proteolysis of Pds1 and mitotic cyclins is mediated by the anaphase-promoting complex (APC). Lagging chromosomes or spindle damage are detected by surveillance mechanisms (checkpoints) which block anaphase onset, cytokinesis and DNA re-replication. Until now, the MAD and BUB genes implicated in this regulation were thought to function in a single pathway that blocks APC activity. We show that spindle damage blocks sister chromatid separation solely by inhibiting APCCdc20-dependent Pds1 proteolysis and that this process requires Mad2. Blocking APCCdh1-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different protein, Bub2. Our data imply that Mad1, Mad2, Mad3 and Bub1 regulate APCCdc20, whereas Bub2 regulates APCCdh1.
D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D007399:Interphase / Q000235:genetics; D008025:Ligases / Q000378:metabolism; D064246:Mad2 Proteins; D008938:Mitosis; D020559:Monomeric GTP-Binding Proteins; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D064249:Securin; D012854:Sister Chromatid Exchange; D008941:Spindle Apparatus / Q000235:genetics*; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D015003:Yeasts