• Open Access

Medical genetics and epigenetics of telomerase

Authors

  • Jillian E. Koziel,

    1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
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  • Melanie J. Fox,

    1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
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  • Catherine E. Steding,

    1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
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  • Alyssa A. Sprouse,

    1. Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA
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  • Brittney-Shea Herbert

    Corresponding author
    1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
    2. Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA
    3. Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA
    4. Indiana University Center for Regenerative Biology and Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
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Correspondence to: Brittney-Shea HERBERT, Indiana University School of Medicine, 975 W Walnut St IB 130, Indianapolis, IN 46202, USA.
 
Tel.: 317–278-6147
Fax: 317–274-1069
E-mail: brherber@iupui.edu

Abstract

  • • Introduction
  • • Epigenetic regulation of telomerase: recent findings beyond transcriptional control
    • - Methylation
    • - Sirtuins
    • - Non-coding RNAs
  • • Consequences of genetic dysfunction of telomerase: medical genetics of telomerase
    • - Dyskeratosis congenita
    • - Aplastic anaemia
    • - Idiopathic pulmonary fibrosis
    • - Acute myeloid leukaemia
  • • TERT and TERC variations and disease predisposition
  • • Summary and perspectives
  • • Acknowledgements

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.

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