Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase

Citation
Mm. Ouellette et al., Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase, J BIOL CHEM, 275(14), 2000, pp. 10072-10076
Citations number
44
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
14
Year of publication
2000
Pages
10072 - 10076
Database
ISI
SICI code
0021-9258(20000407)275:14<10072:STLIFI>2.0.ZU;2-N
Abstract
Human fibroblasts expressing the catalytic component of human telomerase (h TERT) have been followed for 250-400 population doublings, As expected, tel omerase activity declined in long term culture of stable transfectants, Sup prisingly, however, clones with average telomere lengths several kilobases shorter than those of senescent parental cells continued to proliferate. Al though the longest telomeres shortened, the size of the shortest telomeres was maintained. Cells with subsenescent telomere lengths proliferated for a n additional 20 doublings after inhibiting telomerase activity with a domin ant-negative hTERT mutant. These results indicate that, under conditions of limiting telomerase activity, cis-acting signals may recruit telomerase to act on the shortest telomeres, argue against the hypothesis that the morta lity stage 1 mechanism of cellular senescence is regulated by telomere posi tional effects (in which subtelomeric loci silenced by long telomeres are e xpressed when telomeres become short), and suggest that catalytically activ e telomerase is not required to provide a protein-capping role at the end o f very short telomeres.