When chromosomal instability checks mitotic segregation

In most tumor cells a chromosomal instability leads to an abnormal chromoso me number (aneuploidy). The mitotic checkpoint is essential for ensuring ac curate chromosome segregation by allowing mitotic delay in response to a sp indle defect. This checkpoint delays the onset of anaphase until all the ch romosomes are correctly aligned on the mitotic spindle. When unattached kin etochores are present, the metaphase/anaphase transition is not allowed and the time available for chromosome-microtubule capture increases. Genes req uired for this delay were first identified in Saccharomyces cerevisiae (the MAD, BUB and MPS1 genes) and subsequently, homologs have been identified i n higher eucaryotes showing that the spindle checkpoint pathway is highly c onserved. The checkpoint functions by preventing an ubiquitin ligase called the anaphase-promoting complex/cyclosome (AFC) from ubiquitinylating prote ins whose destruction is required for anaphase onset. (C) 2001 Editions sci entifiques et medicales Elsevier SAS.