Stabilization of telomere length and karyotypic stability are directly correlated with the level of hTERT gene expression in primary fibroblasts.
Telomere shortening and lack of telomerase activity have been implicated in cellular senescence in human fibroblasts. Expression of the human telomerase (hTERT) gene in sheep fibroblasts reconstitutes telomerase activity and extends their lifespan. However, telomere length is not maintained in all cell lines, even though in vitro telomerase activity is restored in all of them. Cell lines expressing higher levels of hTERT mRNA do not exhibit telomere erosion or genomic instability. By contrast, fibroblasts expressing lower levels of hTERT do exhibit telomere shortening, although the telomeres eventually stabilize at a shorter length. The shorter telomere lengths and the extent of karyotypic abnormalities are both functions of hTERT expression level. We conclude that telomerase activity is required to bypass senescence but is not sufficient to prevent telomere erosion and genomic instability at lower levels of expression.
Department of Gene Expression and Development, Roslin Institute, Roslin, Midlothian EH25 9PS, United Kingdom.
Wei
W
Cui
Samena
S
Aslam
Judy
J
Fletcher
Diana
D
Wylie
Michael
M
Clinton
A John
AJ
Clark
D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D013997:Time Factors
D004268:DNA-Binding Proteins; D019098:Telomerase