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Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11296-301. Epub 2005 Jul 29.

Generating chromosome instability through the simultaneous deletion of Mad2 and p53.

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1
Department of Biology, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

Cancer cells exhibit high levels of chromosome instability (CIN), and considerable interest surrounds the possibility that inactivation of the spindle checkpoint is involved. However, homozygous disruption of Mad and Bub checkpoint genes in metazoans causes cell death rather than CIN. We now report the isolation and characterization of blastocysts and two independent mouse embryonic fibroblast lines carrying deletions in Mad2 and p53. These cells lack a functional spindle checkpoint, undergo anaphase prematurely, and exhibit an extraordinarily high level of CIN. We conclude that the mitotic checkpoint is not essential for viability per se and that a CIN phenotype can be established in culture through the inactivation of both the Mad2- and p53-dependent checkpoint pathways.

PMID:
16055552
PMCID:
PMC1182134
DOI:
10.1073/pnas.0505053102
[Indexed for MEDLINE]
Free PMC Article
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