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

First Author  Burds AA Year  2005
Journal  Proc Natl Acad Sci U S A Volume  102
Issue  32 Pages  11296-301
PubMed ID  16055552 Mgi Jnum  J:100464
Mgi Id  MGI:3588598 Doi  10.1073/pnas.0505053102
Citation  Burds AA, et al. (2005) Generating chromosome instability through the simultaneous deletion of Mad2 and p53. Proc Natl Acad Sci U S A 102(32):11296-301
abstractText  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.
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