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Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth

Rahman, Ruman; Mo, Ling; Cui, Wei

Authors

Ling Mo

Wei Cui



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 fibro-blasts 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.

Journal Article Type Article
Publication Date Nov 24, 2006
Journal Biochemical and Biophysical Research Communications
Print ISSN 0006-291X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 350
Issue 3
Pages 796-802
APA6 Citation Rahman, R., Mo, L., & Cui, W. (2006). Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth. Biochemical and Biophysical Research Communications, 350(3), 796-802. doi:10.1016/j.bbrc.2006.09.125
DOI https://doi.org/10.1016/j.bbrc.2006.09.125
Keywords hTERT; Telomerase; Telomere; Senescence; Dominant-negative telomerase
Publisher URL https://www.sciencedirect.com/science/article/pii/S0006291X06021826
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