Telomerase: Much Understood, Much More Remains Ripe for Discovery

Main Article Content

Catherine E Steding Samuel Verga

Abstract

Telomerase, the reverse transcriptase responsible for extending the ends of linear chromosomes, has been studied in depth for the past few decades.  Its importance in processes from cellular lifespan to cancer has been well documented.  More recently, it has been exploited as a potential therapeutic target for cancer.   With the development of telomerase inhibitors deemed safe for human use, inhibition of telomerase has become a promising adjuvant therapy capable of improving the therapeutic outcomes of other drugs.  It is within these studies that we now turn to find a new world of previously under-explored territory for telomerase.  Telomerase inhibition has opened the door to new discoveries into how this enzyme functions and what additional effects it might be having in cellular activity and gene regulation.  These new avenues of exploration have the potential to advance our understanding of molecular biology, cellular activity, and even cancer development and progression.  This review will briefly highlight telomerase inhibitors in cancer therapeutics and the role they might be able to play in defining additional non-telomeric activities of telomerase.

Article Details

How to Cite
STEDING, Catherine E; VERGA, Samuel. Telomerase: Much Understood, Much More Remains Ripe for Discovery. Medical Research Archives, [S.l.], n. 2, mar. 2015. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/38>. Date accessed: 21 nov. 2024.
Keywords
telomerase inhibition; telomerase inhibitors; non-telomeric
Section
Review Articles

References

Badrzadeh, F., A. Akbarzadeh, N. Zarghami, M. R. Yamchi, V. Zeighamian, F. S. Tabatabae, M. Taheri, and H. S. Kafil. 2014. "Comparison between effects of free curcumin and curcumin loaded NIPAAm-MAA nanoparticles on telomerase and PinX1 gene expression in lung cancer cells." Asian Pac J Cancer Prev no. 15 (20):8931-6.

Barszczyk, M., P. Buczkowicz, P. Castelo-Branco, S. C. Mack, V. Ramaswamy, J. Mangerel, S. Agnihotri, M. Remke, B. Golbourn, S. Pajovic, C. Elizabeth, M. Yu, B. Luu, A. Morrison, J. Adamski, K. Nethery-Brokx, X. N. Li, T. Van Meter, P. B. Dirks, J. T. Rutka, M. D. Taylor, U. Tabori, and C. Hawkins. 2014. "Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells." Acta Neuropathol no. 128 (6):863-77. doi: 10.1007/s00401-014-1327-6.

Bashash, D., S. H. Ghaffari, R. Mirzaee, K. Alimoghaddam, and A. Ghavamzadeh. 2013. "Telomerase inhibition by non-nucleosidic compound BIBR1532 causes rapid cell death in pre-B acute lymphoblastic leukemia cells." Leuk Lymphoma no. 54 (3):561-8. doi: 10.3109/10428194.2012.704034.

Bashash, D., S. H. Ghaffari, F. Zaker, K. Hezave, M. Kazerani, A. Ghavamzadeh, K. Alimoghaddam, S. A. Mosavi, A. Gharehbaghian, and P. Vossough. 2012. "Direct short-term cytotoxic effects of BIBR 1532 on acute promyelocytic leukemia cells through induction of p21 coupled with downregulation of c-Myc and hTERT transcription." Cancer Invest no. 30 (1):57-64. doi: 10.3109/07357907.2011.629378.

Brennan, S. K., Q. Wang, R. Tressler, C. Harley, N. Go, E. Bassett, C. A. Huff, R. J. Jones, and W. Matsui. 2010. "Telomerase inhibition targets clonogenic multiple myeloma cells through telomere length-dependent and independent mechanisms." PLoS One no. 5 (9). doi: 10.1371/journal.pone.0012487.

Burger, A. M., F. Dai, C. M. Schultes, A. P. Reszka, M. J. Moore, J. A. Double, and S. Neidle. 2005. "The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function." Cancer Res no. 65 (4):1489-96. doi: 10.1158/0008-5472.CAN-04-2910.

Cao, X., C. M. Kong, K. M. Mathi, Y. P. Lim, V. Cacheux-Rataboul, and X. Wang. 2014. "The use of transformed IMR90 cell model to identify the potential extra-telomeric effects of hTERT in cell migration and DNA damage response." BMC Biochem no. 15:17. doi: 10.1186/1471-2091-15-17.

Chang, J. T., Y. L. Chen, H. T. Yang, C. Y. Chen, and A. J. Cheng. 2002. "Differential regulation of telomerase activity by six telomerase subunits." Eur J Biochem no. 269 (14):3442-50.

Chen, H., C. N. Landen, Y. Li, R. D. Alvarez, and T. O. Tollefsbol. 2013. "Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation." Exp Cell Res no. 319 (5):697-706. doi: 10.1016/j.yexcr.2012.12.026.

Chen, X., J. H. Wu, Y. W. Lai, R. Zhao, H. Chao, and L. N. Ji. 2013. "Targeting telomeric G-quadruplexes with the ruthenium(II) complexes [Ru(bpy)(2)(ptpn)](2+) and [Ru(phen)(2)(ptpn)](2+)." Dalton Trans no. 42 (13):4386-97. doi: 10.1039/c3dt32921f.

Cohn, E. P., K. L. Wu, T. R. Pettus, and N. O. Reich. 2012. "A new strategy for detection and development of tractable telomerase inhibitors." J Med Chem no. 55 (8):3678-86. doi: 10.1021/jm201191d.

Cong, Y., and J. W. Shay. 2008. "Actions of human telomerase beyond telomeres." Cell Res no. 18 (7):725-32. doi: 10.1038/cr.2008.74.

Damm, K., U. Hemmann, P. Garin-Chesa, N. Hauel, I. Kauffmann, H. Priepke, C. Niestroj, C. Daiber, B. Enenkel, B. Guilliard, I. Lauritsch, E. Muller, E. Pascolo, G. Sauter, M. Pantic, U. M. Martens, C. Wenz, J. Lingner, N. Kraut, W. J. Rettig, and A. Schnapp. 2001. "A highly selective telomerase inhibitor limiting human cancer cell proliferation." EMBO J no. 20 (24):6958-68. doi: 10.1093/emboj/20.24.6958.

Fakhoury, J., G. A. Nimmo, and C. Autexier. 2007. "Harnessing telomerase in cancer therapeutics." Anticancer Agents Med Chem no. 7 (4):475-83.

Goldblatt, E. M., P. A. Erickson, E. R. Gentry, S. M. Gryaznov, and B. S. Herbert. 2009. "Lipid-conjugated telomerase template antagonists sensitize resistant HER2-positive breast cancer cells to trastuzumab." Breast Cancer Res Treat no. 118 (1):21-32. doi: 10.1007/s10549-008-0201-4.

Goldblatt, E. M., E. R. Gentry, M. J. Fox, S. M. Gryaznov, C. Shen, and B. S. Herbert. 2009. "The telomerase template antagonist GRN163L alters MDA-MB-231 breast cancer cell morphology, inhibits growth, and augments the effects of paclitaxel." Mol Cancer Ther no. 8 (7):2027-35. doi: 10.1158/1535-7163.MCT-08-1188.

Gomez-Millan, J., E. M. Goldblatt, S. M. Gryaznov, M. S. Mendonca, and B. S. Herbert. 2007. "Specific telomere dysfunction induced by GRN163L increases radiation sensitivity in breast cancer cells." Int J Radiat Oncol Biol Phys no. 67 (3):897-905. doi: 10.1016/j.ijrobp.2006.09.038.

Gomez, D. E., R. G. Armando, and D. F. Alonso. 2012. "AZT as a telomerase inhibitor." Front Oncol no. 2:113. doi: 10.3389/fonc.2012.00113.

Greider, C. W., and E. H. Blackburn. 1985. "Identification of a specific telomere terminal transferase activity in Tetrahymena extracts." Cell no. 43 (2 Pt 1):405-13.

Gunaratnam, M., O. Greciano, C. Martins, A. P. Reszka, C. M. Schultes, H. Morjani, J. F. Riou, and S. Neidle. 2007. "Mechanism of acridine-based telomerase inhibition and telomere shortening." Biochem Pharmacol no. 74 (5):679-89. doi: 10.1016/j.bcp.2007.06.011.

Gurung, R. L., H. K. Lim, S. Venkatesan, P. S. Lee, and M. P. Hande. 2014. "Targeting DNA-PKcs and telomerase in brain tumour cells." Mol Cancer no. 13:232. doi: 10.1186/1476-4598-13-232.

Harrison, R. J., A. P. Reszka, S. M. Haider, B. Romagnoli, J. Morrell, M. A. Read, S. M. Gowan, C. M. Incles, L. R. Kelland, and S. Neidle. 2004. "Evaluation of by disubstituted acridone derivatives as telomerase inhibitors: the importance of G-quadruplex binding." Bioorg Med Chem Lett no. 14 (23):5845-9. doi: 10.1016/j.bmcl.2004.09.037.

Herz, C., A. Hertrampf, S. Zimmermann, N. Stetter, M. Wagner, C. Kleinhans, M. Erlacher, J. Schuler, S. Platz, S. Rohn, V. Mersch-Sundermann, and E. Lamy. 2014. "The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC." J Cell Mol Med no. 18 (12):2393-403. doi: 10.1111/jcmm.12412.

Hochreiter, A. E., H. Xiao, E. M. Goldblatt, S. M. Gryaznov, K. D. Miller, S. Badve, G. W. Sledge, and B. S. Herbert. 2006. "Telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth, and metastasis of breast cancer." Clin Cancer Res no. 12 (10):3184-92. doi: 10.1158/1078-0432.CCR-05-2760.

Hu, Y., D. Bobb, Y. Lu, J. He, and J. S. Dome. 2014. "Effect of telomerase inhibition on preclinical models of malignant rhabdoid tumor." Cancer Genet no. 207 (9):403-11. doi: 10.1016/j.cancergen.2014.09.002.

Jaiswal, R. K., P. Kumar, and P. K. Yadava. 2013. "Telomerase and its extracurricular activities." Cell Mol Biol Lett no. 18 (4):538-54. doi: 10.2478/s11658-013-0105-0.

Jeoung, J. Y., H. Y. Nam, J. Kwak, H. J. Jin, H. J. Lee, B. W. Lee, J. H. Baek, J. S. Eom, E. Chang, D. Shin, S. J. Choi, and S. W. Kim. 2014. "A Decline in Wnt3a Signaling is Necessary for Mesenchymal Stem Cells to Proceed to Replicative Senescence." Stem Cells Dev. doi: 10.1089/scd.2014.0273.

Joseph, I., R. Tressler, E. Bassett, C. Harley, C. M. Buseman, P. Pattamatta, W. E. Wright, J. W. Shay, and N. F. Go. 2010. "The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines." Cancer Res no. 70 (22):9494-504. doi: 10.1158/0008-5472.CAN-10-0233.

Kazemi-Lomedasht, F., A. Rami, and N. Zarghami. 2013. "Comparison of inhibitory effect of curcumin nanoparticles and free curcumin in human telomerase reverse transcriptase gene expression in breast cancer." Adv Pharm Bull no. 3 (1):127-30. doi: 10.5681/apb.2013.021.

Koziel, J. E., and B. S. Herbert. 2015. "The telomerase inhibitor imetelstat alone, and in combination with trastuzumab, decreases the cancer stem cell population and self-renewal of HER2 breast cancer cells." Breast Cancer Res Treat. doi: 10.1007/s10549-015-3270-1.

Lackner, D. H., M. T. Hayashi, A. J. Cesare, and J. Karlseder. 2014. "A genomics approach identifies senescence-specific gene expression regulation." Aging Cell no. 13 (5):946-50. doi: 10.1111/acel.12234.

Li, Q., J. Zhang, L. Yang, Q. Yu, Q. Chen, X. Qin, F. Le, Q. Zhang, and J. Liu. 2014. "Stabilization of G-quadruplex DNA and inhibition of telomerase activity studies of ruthenium(II) complexes." J Inorg Biochem no. 130:122-9. doi: 10.1016/j.jinorgbio.2013.10.006.

Liao, G., X. Chen, J. Wu, C. Qian, H. Wang, L. Ji, and H. Chao. 2014. "Novel ruthenium(II) polypyridyl complexes as G-quadruplex stabilisers and telomerase inhibitors." Dalton Trans no. 43 (21):7811-9. doi: 10.1039/c3dt53547a.

Liao, G., X. Chen, J. Wu, C. Qian, Y. Wang, L. Ji, and H. Chao. 2015. "Ruthenium(ii) polypyridyl complexes as dual inhibitors of telomerase and topoisomerase." Dalton Trans. doi: 10.1039/c4dt03585b.

Listerman, I., F. S. Gazzaniga, and E. H. Blackburn. 2014. "An investigation of the effects of the core protein telomerase reverse transcriptase on Wnt signaling in breast cancer cells." Mol Cell Biol no. 34 (2):280-9. doi: 10.1128/MCB.00844-13.

Long, S., D. J. Argyle, E. A. Gault, and L. Nasir. 2007. "Inhibition of telomerase in canine cancer cells following telomestatin treatment." Vet Comp Oncol no. 5 (2):99-107. doi: 10.1111/j.1476-5829.2006.00118.x.
Maida, Y., and K. Masutomi. 2011. "RNA-dependent RNA polymerases in RNA silencing." Biol Chem no. 392 (4):299-304. doi: 10.1515/BC.2011.035.

Marian, C. O., S. K. Cho, B. M. McEllin, E. A. Maher, K. J. Hatanpaa, C. J. Madden, B. E. Mickey, W. E. Wright, J. W. Shay, and R. M. Bachoo. 2010. "The telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor-initiating cells leading to decreased proliferation and tumor growth." Clin Cancer Res no. 16 (1):154-63. doi: 10.1158/1078-0432.CCR-09-2850.

Masutomi, K., R. Possemato, J. M. Wong, J. L. Currier, Z. Tothova, J. B. Manola, S. Ganesan, P. M. Lansdorp, K. Collins, and W. C. Hahn. 2005. "The telomerase reverse transcriptase regulates chromatin state and DNA damage responses." Proc Natl Acad Sci U S A no. 102 (23):8222-7. doi: 10.1073/pnas.0503095102.

Mender, I., S. Senturk, N. Ozgunes, K. C. Akcali, D. Kletsas, S. Gryaznov, A. Can, J. W. Shay, and Z. G. Dikmen. 2013. "Imetelstat (a telomerase antagonist) exerts offtarget effects on the cytoskeleton." Int J Oncol no. 42 (5):1709-15. doi: 10.3892/ijo.2013.1865.
Nakashima, M., J. Nandakumar, K. D. Sullivan, J. M. Espinosa, and T. R. Cech. 2013. "Inhibition of telomerase recruitment and cancer cell death." J Biol Chem no. 288 (46):33171-80. doi: 10.1074/jbc.M113.518175.

Park, J. I., A. S. Venteicher, J. Y. Hong, J. Choi, S. Jun, M. Shkreli, W. Chang, Z. Meng, P. Cheung, H. Ji, M. McLaughlin, T. D. Veenstra, R. Nusse, P. D. McCrea, and S. E. Artandi. 2009. "Telomerase modulates Wnt signalling by association with target gene chromatin." Nature no. 460 (7251):66-72. doi: 10.1038/nature08137.

Perez, C. A., E. S. Santos, B. A. Arango, L. E. Raez, and E. E. Cohen. 2012. "Novel molecular targeted therapies for refractory thyroid cancer." Head Neck no. 34 (5):736-45. doi: 10.1002/hed.21755.

Ray, S., Z. Karamysheva, L. Wang, D. E. Shippen, and C. M. Price. 2002. "Interactions between telomerase and primase physically link the telomere and chromosome replication machinery." Mol Cell Biol no. 22 (16):5859-68.

Roth, A., C. B. Harley, and G. M. Baerlocher. 2010. "Imetelstat (GRN163L)--telomerase-based cancer therapy." Recent Results Cancer Res no. 184:221-34. doi: 10.1007/978-3-642-01222-8_16.

Ruden, M., and N. Puri. 2013. "Novel anticancer therapeutics targeting telomerase." Cancer Treat Rev no. 39 (5):444-56. doi: 10.1016/j.ctrv.2012.06.007.

Sabokrouh, A., M. T. Goodarzi, A. Vaisi-Raygani, S. Khatami, and M. Taghizadeh-Jahed. 2014. "Effects of treatment with platinum azidothymidine and azidothymidine on telomerase activity and bcl-2 concentration in hepatocellular carcinoma- induced rats." Avicenna J Med Biotechnol no. 6 (4):200-9.
Santos, J. H., J. N. Meyer, M. Skorvaga, L. A. Annab, and B. Van Houten. 2004. "Mitochondrial hTERT exacerbates free-radical-mediated mtDNA damage." Aging Cell no. 3 (6):399-411. doi: 10.1111/j.1474-9728.2004.00124.x.

Seimiya, H., T. Oh-hara, T. Suzuki, I. Naasani, T. Shimazaki, K. Tsuchiya, and T. Tsuruo. 2002. "Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors MST-312, MST-295, and MST-1991." Mol Cancer Ther no. 1 (9):657-65.

Serrano, D., A. M. Bleau, I. Fernandez-Garcia, T. Fernandez-Marcelo, P. Iniesta, C. Ortiz-de-Solorzano, and A. Calvo. 2011. "Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer." Mol Cancer no. 10:96. doi: 10.1186/1476-4598-10-96.

Sharma, G. G., A. Gupta, H. Wang, H. Scherthan, S. Dhar, V. Gandhi, G. Iliakis, J. W. Shay, C. S. Young, and T. K. Pandita. 2003. "hTERT associates with human telomeres and enhances genomic stability and DNA repair." Oncogene no. 22 (1):131-46. doi: 10.1038/sj.onc.1206063.

Sharma, G. G., K. K. Hwang, R. K. Pandita, A. Gupta, S. Dhar, J. Parenteau, M. Agarwal, H. J. Worman, R. J. Wellinger, and T. K. Pandita. 2003. "Human heterochromatin protein 1 isoforms HP1(Hsalpha) and HP1(Hsbeta) interfere with hTERT-telomere interactions and correlate with changes in cell growth and response to ionizing radiation." Mol Cell Biol no. 23 (22):8363-76.

Smith, L. L., H. A. Coller, and J. M. Roberts. 2003. "Telomerase modulates expression of growth-controlling genes and enhances cell proliferation." Nat Cell Biol no. 5 (5):474-9. doi: 10.1038/ncb985.

Sprouse, A. A., C. E. Steding, and B. S. Herbert. 2012. "Pharmaceutical regulation of telomerase and its clinical potential." J Cell Mol Med no. 16 (1):1-7. doi: 10.1111/j.1582-4934.2011.01460.x.

Strahl, C., and E. H. Blackburn. 1996. "Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human cell lines." Mol Cell Biol no. 16 (1):53-65.

Tauchi, T., K. Shin-ya, G. Sashida, M. Sumi, S. Okabe, J. H. Ohyashiki, and K. Ohyashiki. 2006. "Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia." Oncogene no. 25 (42):5719-25. doi: 10.1038/sj.onc.1209577.

Tippani, R., L. J. Prakhya, M. Porika, K. Sirisha, S. Abbagani, and C. Thammidala. 2014. "Pterostilbene as a potential novel telomerase inhibitor: molecular docking studies and its in vitro evaluation." Curr Pharm Biotechnol no. 14 (12):1027-35.

Tsai, Y. C., H. Qi, C. P. Lin, R. K. Lin, J. E. Kerrigan, S. G. Rzuczek, E. J. LaVoie, J. E. Rice, D. S. Pilch, Y. L. Lyu, and L. F. Liu. 2009. "A G-quadruplex stabilizer induces M-phase cell cycle arrest." J Biol Chem no. 284 (34):22535-43. doi: 10.1074/jbc.M109.020230.

Wang, Y., C. Sun, A. Mao, X. Zhang, X. Zhou, Z. Wang, and H. Zhang. 2015. "Radiosensitization to X-ray radiation by telomerase inhibitor MST-312 in human hepatoma HepG2 cells." Life Sci. doi: 10.1016/j.lfs.2014.12.027.

Ward, R. J., and C. Autexier. 2005. "Pharmacological telomerase inhibition can sensitize drug-resistant and drug-sensitive cells to chemotherapeutic treatment." Mol Pharmacol no. 68 (3):779-86. doi: 10.1124/mol.105.011494.

Wardi, L., N. Alaaeddine, I. Raad, R. Sarkis, R. Serhal, C. Khalil, and G. Hilal. 2014. "Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532." Cancer Cell Int no. 14:60. doi: 10.1186/1475-2867-14-60.

Wong, V. C., A. Morrison, U. Tabori, and C. E. Hawkins. 2010. "Telomerase inhibition as a novel therapy for pediatric ependymoma." Brain Pathol no. 20 (4):780-6. doi: 10.1111/j.1750-3639.2010.00372.x.

Wu, X., S. Smavadati, K. Nordfjall, K. Karlsson, F. Qvarnstrom, M. Simonsson, M. Bergqvist, S. Gryaznov, S. Ekman, and Y. Paulsson-Karlsson. 2012. "Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks." Biochim Biophys Acta no. 1823 (12):2130-5. doi: 10.1016/j.bbamcr.2012.08.003.

Yaku, H., T. Murashima, D. Miyoshi, and N. Sugimoto. 2014. "In vitro assays predictive of telomerase inhibitory effect of G-quadruplex ligands in cell nuclei." J Phys Chem B no. 118 (10):2605-14. doi: 10.1021/jp410669t.

Yu, L., S. Liu, C. Zhang, B. Zhang, B. M. Simoes, R. Eyre, Y. Liang, H. Yan, Z. Wu, W. Guo, and R. B. Clarke. 2013. "Enrichment of human osteosarcoma stem cells based on hTERT transcriptional activity." Oncotarget no. 4 (12):2326-38.

Yu, Q., Y. Liu, C. Wang, D. Sun, X. Yang, Y. Liu, and J. Liu. 2012. "Chiral ruthenium(II) polypyridyl complexes: stabilization of g-quadruplex DNA, inhibition of telomerase activity and cellular uptake." PLoS One no. 7 (12):e50902. doi: 10.1371/journal.pone.0050902.

Yu, Q., Y. Liu, L. Xu, C. Zheng, F. Le, X. Qin, Y. Liu, and J. Liu. 2014. "Ruthenium(II) polypyridyl complexes: cellular uptake, cell image and apoptosis of HeLa cancer cells induced by double targets." Eur J Med Chem no. 82:82-95. doi: 10.1016/j.ejmech.2014.05.040.

Yu, Q., Y. Liu, J. Zhang, F. Yang, D. Sun, D. Liu, Y. Zhou, and J. Liu. 2013. "Ruthenium(II) polypyridyl complexes as G-quadruplex inducing and stabilizing ligands in telomeric DNA." Metallomics no. 5 (3):222-31. doi: 10.1039/c3mt20214c.

Zhang, W., P. Yang, F. Gao, J. Yang, and K. Yao. 2014. "Effects of epigallocatechin gallate on the proliferation and apoptosis of the nasopharyngeal carcinoma cell line CNE2." Exp Ther Med no. 8 (6):1783-1788. doi: 10.3892/etm.2014.2020.

Zhihua, Z., S. Miaomiao, Y. Jianping, and C. Kuisheng. 2014. "Research for the influence of telomerase inhibitors on myeloma cell and therapy." Pak J Pharm Sci no. 27 (5 Suppl):1641-4.

Zhou, J., D. Ding, M. Wang, and Y. S. Cong. 2014. "Telomerase reverse transcriptase in the regulation of gene expression." BMB Rep no. 47 (1):8-14.

Zhuang, X. Y., and Y. G. Yao. 2013. "Mitochondrial dysfunction and nuclear-mitochondrial shuttling of TERT are involved in cell proliferation arrest induced by G-quadruplex ligands." FEBS Lett no. 587 (11):1656-62. doi: 10.1016/j.febslet.2013.04.010.