Telomere

Grazia D Raffa, Sapienza University of Rome, Rome, Italy
Giovanni Cenci, Sapienza University of Rome, Rome, Italy

Published online: April 2015

DOI: 10.1002/9780470015902.a0005787.pub3

Abstract

Telomeres are specialised structures that protect chromosome ends from degradation and fusion events. In most eukaryotes, including yeast and mammals, telomeric DNA consists of short, repetitive G‐rich sequences, which end with 3′ G‐rich overhangs and are elongated by the specialised reverse transcriptase telomerase. Telomeric repeats are bound by several DNA‐binding proteins, which regulate telomerase activity and protect (cap) chromosome ends from degradation and inappropriate DNA repair. If uncapped, telomeres are sensed as DNA breaks and undergo unwanted DNA repair, which can eventually lead to the activation of cell cycle checkpoints and/or to end‐to‐end fusion. The dicentric chromosomes generated by telomeric fusion can cause non‐disjunction and chromosome breakage during anaphase. These events result in loss of genetic material and chromosome rearrangements that in mammals might lead to several diseases including cancer. Thus, it has become evident that telomeres play critical roles in the maintenance of genome stability.

Key Concepts

  • Telomeres are required for chromosome end maintenance and genome stability.
  • Telomeres are special chromatin architectures found at the end of linear chromosomes
  • Telomeres protects chromosome ends from degradation and fusion events
  • Telomeric DNA consists of tandem repeats that are bound by several DNA-binding proteins
  • Critically short telomeres become dysfunctional and eventually lead to chromosome fusions and cell death

Keywords: telomeres; telomeric proteins; telomeric fusions; telomere capping; DNA damage checkpoint; telomere dysfunction

Figure 1. Telomere capping complexes in different species. In mammals, the six‐member shelterin complex associates with both single‐ and double‐stranded regions of the telomeric DNA. S. cerevisiae telomeres are protected by the trimeric Cdc13/Stn1/Ten1 (CST) complex, which assembles on the G‐overhang. The Rap1/Rif1/Rif2 complex binds the duplex region of the budding yeast telomere. S. pombe telomeres are bound by a shelterin‐like complex. In addition, Stn1 and Ten1 contribute to chromosome end protection, but it is not known how they interact with other telomere proteins. D. melanogaster Terminin contains the fast evolving proteins HipHop, HOAP, Moi and Ver. Ver is structurally related to human Stn1 and binds ss‐DNA. In A. Thaliana, CST functions as the major telomere capping complex. POT1a is a telomerase accessory factor and is not required for chromosome end protection.
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Further Reading

Blasco MA (2007) The epigenetic regulation of mammalian telomeres. Nature Reviews Genetics 8: 299–309.

Dehe PM and Cooper JP (2010) Fission yeast telomeres forecast the end of the crisis. FEBS Letters 584: 3725–33.

Denchi EL (2009) Give me a break: how telomeres suppress the DNA damage response. DNA Repair (Amst) 8: 1118–26.

Kazda A , Zellinger B , Rossler M , et al. (2012) Chromosome end protection by blunt‐ended telomeres. Genes and Development 26: 1703–13.

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Nelson AD and Shippen DE (2012) Blunt‐ended telomeres: an alternative ending to the replication and end protection stories. Genes and Development 26: 1648–52.

Rog O and Cooper JP (2008) Telomeres in drag: dressing as DNA damage to engage telomerase. Current Opinion in Genetics and Development 18: 212–20.

Sfeir A and de Lange T (2012) Removal of shelterin reveals the telomere end‐protection problem. Science 336: 593–7.

Verdun RE and Karlseder J (2007) Replication and protection of telomeres. Nature 447: 924–31.

Zakian VA (2012) Telomeres: the beginnings and ends of eukaryotic chromosomes. Experimental Cell Research 318: 1456–60.

Related Sub-Topics:

Cell Death and Cellular Senescence | Mechanisms of Cell Death, Senescence and Metabolism | Nucleic Acid Structure | DNA Structure and Function | Basic Cell Biology, Protein, RNA and DNA | Chromosomes and Chromatin Modifications | DNA Damage and Repair
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Article Title: Telomere
 
How to Cite close
Raffa, Grazia D, and Cenci, Giovanni(Apr 2015) Telomere. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005787.pub3]