The spindle checkpoint and chromosomal stability.

Normal human somatic cells contain 46 chromosomes (22 pairs of autosomes and two sex chromosomes). Chromosome missegregation leads to abnormal numbers of chromosomes or aneuploidy. This form of genetic instability alters the dosages of large subsets of genes, which can result in severe disease phenotypes. Most human cancer cells are aneuploid. It is generally believed that aneuploidy contributes to cancer formation. The spindle checkpoint is a cell-cycle surveillance mechanism that ensures the fidelity of chromosome segregation during mitosis and meiosis. In this article, we review our current understanding of the molecular basis of the spindle checkpoint and the recent evidence that links the malfunction of this checkpoint to aneuploidy and tumorigenesis.