Zhu J, Wang H, Bishop J M, Blackburn E H
The G. W. Hooper Foundation, University of California, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3723-8. doi: 10.1073/pnas.96.7.3723.
Human fibroblasts whose lifespan in culture has been extended by expression of a viral oncogene eventually undergo a growth crisis marked by failure to proliferate. It has been proposed that telomere shortening in these cells is the property that limits their proliferation. Here we report that ectopic expression of the wild-type reverse transcriptase protein (hTERT) of human telomerase averts crisis, at the same time reducing the frequency of dicentric and abnormal chromosomes. Surprisingly, as the resulting immortalized cells containing active telomerase continue to proliferate, their telomeres continue to shorten to mean lengths below those in control cells that enter crisis. These results provide evidence for a protective function of human telomerase that allows cell proliferation without requiring net lengthening of telomeres.
通过表达病毒癌基因而延长了体外培养寿命的人成纤维细胞最终会经历以增殖失败为特征的生长危机。有人提出,这些细胞中的端粒缩短是限制其增殖的特性。在此我们报告,人端粒酶野生型逆转录酶蛋白(hTERT)的异位表达可避免危机,同时降低双着丝粒染色体和异常染色体的频率。令人惊讶的是,由于产生的含有活性端粒酶的永生化细胞继续增殖,它们的端粒继续缩短至低于进入危机的对照细胞中的平均长度。这些结果为人类端粒酶的保护功能提供了证据,该功能允许细胞增殖而无需端粒的净延长。