Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth.
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Rahman R, Mo L, Cui W
Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth.
Biochem Biophys Res Commun. 2006 Nov 24;350(3):796-802. Epub 2006 Sep 29.
- PubMed ID
- 17026956 [ View in PubMed]
- Abstract
Telomerase catalytic subunit (TERT) seems a key factor controlling telomerase activity, telomere length, and cell growth. To further address this issue, we forced expression of a catalytically inactive mutant human TERT (hTERT) in hTERT-immortalised sheep fibroblasts to examine its effects. Expression of mutant hTERT compromised telomerase activity reconstituted by wild-type hTERT in a manner directly attributable to mutant hTERT expression level. High levels of mutant hTERT expression inhibited cell growth with a subset of cells entering replicative senescence. Furthermore, significant telomere attrition was evident in two of three clones with high levels of mutant hTERT expression. Our findings are consistent with the notion that hTERT homodimers are necessarily required to form a functional telomerase complex at the telomere substrate. We also highlight the requirement of a more thorough understanding of telomerase- and telomere-associated factors to understand fully the interplay that governs telomere homeostasis in vitro and in vivo.