Generating chromosome instability through the simultaneous deletion of Mad2 and p53
Generating chromosome instability through the simultaneous deletion of Mad2 and p53
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DOI：
10.1073/pnas.0505053102
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发表时间：
2005-08-09
影响因子：
11.1
通讯作者：
Sorger, PK
中科院分区：
文献类型：
--
作者：
Burds, AA;Lutum, AS;Sorger, PK
癌细胞表现出高水平的染色体不稳定性（CIN），并且相当大的兴趣围绕着涉及纺锤体检查点失活的可能性。然而，多细胞动物中Mad和Bub检查点基因的纯合破坏导致细胞死亡而不是CIN。我们现在报告的分离和表征囊胚和两个独立的小鼠胚胎成纤维细胞株携带Mad2和p53缺失。这些细胞缺乏功能性纺锤体检查点，过早地经历后期，并表现出非常高的CIN水平。我们的结论是，有丝分裂检查点本身的生存能力是不必要的，CIN表型可以通过Mad2和p53依赖的检查点途径的失活在文化中建立。
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.