Medical Genetics and Epigenetics of Telomerase

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2011 Feb 18

PMID 21323862

Citations 18

Authors

Jillian E Koziel

Melanie J Fox

Catherine E Steding

Alyssa A Sprouse

Brittney-Shea Herbert

Affiliations

Soon will be listed here.

Abstract

Telomerase is a specialized reverse transcriptase that extends and maintains the terminal ends of chromosomes, or telomeres. Since its discovery in 1985 by Nobel Laureates Elizabeth Blackburn and Carol Greider, thousands of articles have emerged detailing its significance in telomere function and cell survival. This review provides a current assessment on the importance of telomerase regulation and relates it in terms of medical genetics. In this review, we discuss the recent findings on telomerase regulation, focusing on epigenetics and non-coding RNAs regulation of telomerase, such as microRNAs and the recently discovered telomeric-repeat containing RNA transcripts. Human genetic disorders that develop due to mutations in telomerase subunits, the role of single nucleotide polymorphisms in genes encoding telomerase components and diseases as a result of telomerase regulation going awry are also discussed. Continual investigation of the complex regulation of telomerase will further our insight into the use of controlling telomerase activity in medicine.

Citing Articles

Epigenetics in Alzheimer's Disease: A Critical Overview.

Villa C, Combi R Int J Mol Sci. 2024; 25(11).

PMID: 38892155 PMC: 11173284. DOI: 10.3390/ijms25115970.

A phase 1 trial of human telomerase reverse transcriptase (hTERT) vaccination combined with therapeutic strategies to control immune-suppressor mechanisms.

Zareian N, Eremin O, Pandha H, Baird R, Kwatra V, Funingana G Exp Biol Med (Maywood). 2024; 249:10021.

PMID: 38463391 PMC: 10911124. DOI: 10.3389/ebm.2024.10021.

Gene Modification Using CRISPR-dCas9-dnmt3a System as a Therapeutic Approach Against Glioma.

Taghavi Rad F, Ghorbian S, Naghavi Gargari B, Shirvani Farsani Z, Sharifi R Iran J Pharm Res. 2023; 22(1):e137226.

PMID: 38116572 PMC: 10728856. DOI: 10.5812/ijpr-137226.

The importance of pseudouridylation: human disorders related to the fifth nucleoside.

Keszthelyi T, Tory K Biol Futur. 2023; 74(1-2):3-15.

PMID: 37000312 DOI: 10.1007/s42977-023-00158-3.

Sirtuins and redox signaling interplay in neurogenesis, neurodegenerative diseases, and neural cell reprogramming.

Mormone E, Iorio E, Abate L, Rodolfo C Front Neurosci. 2023; 17:1073689.

PMID: 36816109 PMC: 9929468. DOI: 10.3389/fnins.2023.1073689.

References

Carroll K, Ly H . Telomere dysfunction in human diseases: the long and short of it!. Int J Clin Exp Pathol. 2009; 2(6):528-43. PMC: 2713453. View

Nam E, Yoon H, Kim S, Kim H, Kim Y, Kim J . MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 2008; 14(9):2690-5. DOI: 10.1158/1078-0432.CCR-07-1731. View

Lanzilli G, Fuggetta M, Tricarico M, Cottarelli A, Serafino A, Falchetti R . Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro. Int J Oncol. 2006; 28(3):641-8. View

Vulliamy T, Marrone A, Dokal I, Mason P . Association between aplastic anaemia and mutations in telomerase RNA. Lancet. 2002; 359(9324):2168-70. DOI: 10.1016/S0140-6736(02)09087-6. View

Vulliamy T, Marrone A, Knight S, Walne A, Mason P, Dokal I . Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood. 2005; 107(7):2680-5. DOI: 10.1182/blood-2005-07-2622. View

Jin G, Xu L, Shu Y, Tian T, Liang J, Xu Y . Common genetic variants on 5p15.33 contribute to risk of lung adenocarcinoma in a Chinese population. Carcinogenesis. 2009; 30(6):987-90. DOI: 10.1093/carcin/bgp090. View

Koturbash I, Zemp F, Pogribny I, Kovalchuk O . Small molecules with big effects: the role of the microRNAome in cancer and carcinogenesis. Mutat Res. 2010; 722(2):94-105. DOI: 10.1016/j.mrgentox.2010.05.006. View

Martinez P, Blasco M . Role of shelterin in cancer and aging. Aging Cell. 2010; 9(5):653-66. DOI: 10.1111/j.1474-9726.2010.00596.x. View

Makarov V, Hirose Y, Langmore J . Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell. 1997; 88(5):657-66. DOI: 10.1016/s0092-8674(00)81908-x. View

10.

Deville L, Hillion J, Segal-Bendirdjian E . Telomerase regulation in hematological cancers: a matter of stemness?. Biochim Biophys Acta. 2009; 1792(4):229-39. DOI: 10.1016/j.bbadis.2009.01.016. View

11.

Liu L, Lai S, Andrews L, Tollefsbol T . Genetic and epigenetic modulation of telomerase activity in development and disease. Gene. 2004; 340(1):1-10. DOI: 10.1016/j.gene.2004.06.011. View

12.

Mushiroda T, Wattanapokayakit S, Takahashi A, Nukiwa T, Kudoh S, Ogura T . A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J Med Genet. 2008; 45(10):654-6. DOI: 10.1136/jmg.2008.057356. View

13.

Robart A, Collins K . Investigation of human telomerase holoenzyme assembly, activity, and processivity using disease-linked subunit variants. J Biol Chem. 2009; 285(7):4375-86. PMC: 2836042. DOI: 10.1074/jbc.M109.088575. View

14.

Zienolddiny S, Skaug V, Landvik N, Ryberg D, Phillips D, Houlston R . The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung. Carcinogenesis. 2009; 30(8):1368-71. DOI: 10.1093/carcin/bgp131. View

15.

Codd V, Mangino M, van der Harst P, Braund P, Kaiser M, Beveridge A . Common variants near TERC are associated with mean telomere length. Nat Genet. 2010; 42(3):197-9. PMC: 3773906. DOI: 10.1038/ng.532. View

16.

Liu Z, Li G, Wei S, Niu J, Wang L, Sturgis E . Genetic variations in TERT-CLPTM1L genes and risk of squamous cell carcinoma of the head and neck. Carcinogenesis. 2010; 31(11):1977-81. PMC: 2966556. DOI: 10.1093/carcin/bgq179. View

17.

Fogarty P, Yamaguchi H, Wiestner A, Baerlocher G, Sloand E, Zeng W . Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA. Lancet. 2003; 362(9396):1628-30. DOI: 10.1016/S0140-6736(03)14797-6. View

18.

Nittis T, Guittat L, Stewart S . Alternative lengthening of telomeres (ALT) and chromatin: is there a connection?. Biochimie. 2007; 90(1):5-12. DOI: 10.1016/j.biochi.2007.08.009. View

19.

Baur J . Biochemical effects of SIRT1 activators. Biochim Biophys Acta. 2009; 1804(8):1626-34. PMC: 2886178. DOI: 10.1016/j.bbapap.2009.10.025. View

20.

Steck P, Ligon A, Cheong P, Yung W, Pershouse M . Two tumor suppressive loci on chromosome 10 involved in human glioblastomas. Genes Chromosomes Cancer. 1995; 12(4):255-61. DOI: 10.1002/gcc.2870120404. View