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The spindle checkpoint, aneuploidy, and cancer

Oncogene volume 23, pages 2016–2027 (2004)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr Forrest Spencer for communicating results prior to publication and members of the Yu laboratory for helpful discussion. HY is the Michael L Rosenberg Scholar in Biomedical Research. Research in our laboratory is supported by the National Institutes of Health (GM61542), the Packard Foundation, the Burroughs Wellcome Fund, the Robert A Welch Foundation (I-1441), the March of Dimes Foundation, the Leukemia and Lyophoma Society, and the WM Keck Foundation.

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  1. Department of Pharmacology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, 75390-9041, TX, USA

    Rajnish Bharadwaj & Hongtao Yu

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Bharadwaj, R., Yu, H. The spindle checkpoint, aneuploidy, and cancer. Oncogene 23, 2016–2027 (2004). https://doi.org/10.1038/sj.onc.1207374

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