The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability

被引:931
作者
Hemann, MT
Strong, MA
Hao, LY
Greider, CW [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Grad Training Program Human Genet, Baltimore, MD 21205 USA
关键词
D O I
10.1016/S0092-8674(01)00504-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Loss of telomere function can induce cell cycle arrest and apoptosis. To investigate the processes that trigger cellular responses to telomere dysfunction, we crossed mTR-/- G6 mice that have short telomeres with mice heterozygous for telomerase (mTR+/-) that have long telomeres. The phenotype of the telomerase null offspring was similar to that of the late generation parent, although only half of the chromosomes were short. Strikingly, spectra[ karyotyping (SKY) analysis revealed that loss of telomere function occurred preferentially on chromosomes with critically short telomeres. Our data indicate that, while average telomere length is measured in most studies, it is not the average but rather the shortest telomeres that constitute telomere dysfunction and limit cellular survival in the absence of telomerase.
引用
收藏
页码:67 / 77
页数:11
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