The spindle checkpoint, aneuploidy, and cancer

Oncogene. 2004 Mar 15;23(11):2016-27. doi: 10.1038/sj.onc.1207374.


Cancer cells contain abnormal number of chromosomes (aneuploidy), which is a prevalent form of genetic instability in human cancers. Defects in a cell cycle surveillance mechanism called the spindle checkpoint contribute to chromosome instability and aneuploidy. In response to straying chromosomes in mitosis, the spindle checkpoint inhibits the ubiquitin ligase activity of the anaphase-promoting complex or cyclosome (APC/C), thus preventing precocious chromosome segregation and ensuring the accurate partition of the genetic material. We review recent progress toward the understanding of the molecular mechanism of the spindle checkpoint and its role in guarding genome integrity at the chromosome level.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Motifs
  • Aneuploidy*
  • Animals
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Chromosome Segregation
  • Humans
  • Kinetochores / metabolism
  • Models, Biological
  • Neoplasms / genetics*
  • Protein Structure, Tertiary
  • Spindle Apparatus*


  • Cell Cycle Proteins