Increasing evidence from research on telomerase suggests that in addition to its catalytic telomere
repeat synthesis activity, telomerase may have other biologically important functions. The canonical
roles of telomerase are at the telomere ends where they elongate telomeres and maintain genomic
stability and cellular lifespan. The catalytic protein component Telomerase Reverse Transcriptase
(TERT) is preferentially expressed at high levels in cancer cells despite the existence of an alternative
mechanism for telomere maintenance (alternative lengthening of telomeres or ALT). TERT is also expressed
at higher levels than necessary for maintaining functional telomere length, suggesting other possible
adaptive functions. Emerging non-canonical roles of TERT include regulation of non-telomeric
DNA damage responses, promotion of cell growth and proliferation, acceleration of cell cycle kinetics,
and control of mitochondrial integrity following oxidative stress. Non-canonical activities of TERT primarily
show cellular protective effects, and nuclear TERT has been shown to protect against cell death
following double-stranded DNA damage, independent of its role in telomere length maintenance. TERT
has been suggested to act as a chromatin modulator and participate in the transcriptional regulation of
gene expression. TERT has also been reported to regulate transcript levels through an RNA-dependent
RNA Polymerase (RdRP) activity and produce siRNAs in a Dicer-dependent manner. At the mitochondria,
TERT is suggested to protect against oxidative stress-induced mtDNA damage and promote mitochondrial
integrity. These extra-telomeric functions of TERT may be advantageous in the context of increased
proliferation and metabolic stress often found in rapidly-dividing cancer cells. Understanding
the spectrum of non-canonical functions of telomerase may have important implications for the rational
design of anti-cancer chemotherapeutic drugs.
Computational Study of the Interactions between Antimalarial Chemotherapies with Folate Pathway Receptors and Telomerase Reverse Transcriptase
