Telomere

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. 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. 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. Terminin contains the fast evolving proteins HipHop, HOAP, Moi and Ver. Ver is structurally related to human Stn1 and binds ss‐DNA. In , 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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References

Azzalin CM and Lingner J (2014) Telomere functions grounding on TERRA firma. Trends in Cell Biology 25: 29–36.

Cenci G (2009) Drosophila cell cycle under arrest: uncapped telomeres plead guilty. Cell Cycle 8: 990–5.

Doksani Y and de Lange T (2014) The role of double‐strand break repair pathways at functional and dysfunctional telomeres. Cold Spring Harbor Perspectives in Biology 6: a016576.

Flynn RL and Zou L (2010) Oligonucleotide/oligosaccharide‐binding fold proteins: a growing family of genome guardians. Critical Reviews in Biochemistry and Molecular Biology 45: 266–75.

Giraud‐Panis MJ , Teixeira MT , Geli V and Gilson E (2010) CST meets shelterin to keep telomeres in check. Molecular Cell 39: 665–76.

Griffith JD , Comeau L , Rosenfield S , et al. (1999) Mammalian telomeres end in a large duplex loop. Cell 97: 503–514.

Jain D and Cooper JP (2010) Telomeric strategies: means to an end. Annual Review of Genetics 44: 243–69.

Jain D , Hebden AK , Nakamura TM , Miller KM and Cooper JP (2010) HAATI survivors replace canonical telomeres with blocks of generic heterochromatin. Nature 467: 223–7.

Longhese MP (2008) DNA damage response at functional and dysfunctional telomeres. Genes and Development 22: 125–40.

Madalena CR , Fernandes T , Villasante A and Gorab E (2010) Curiously composite structures of a retrotransposon and a complex repeat associated with chromosome ends of Rhynchosciara americana (Diptera: Sciaridae). Chromosome Research 18: 587–98.

Mason JM , Frydrychova RC and Biessmann H (2008) Drosophila telomeres: an exception providing new insights. Bioessays 30: 25–37.

McClintock B (1939) The behavior in successive nuclear divisions of a chromosome broken at meiosis. Proceedings of the National Academy of Sciences of the United States of America 25: 405–16.

Musarò M , Ciapponi L , Fasulo B , Gatti M and Cenci G (2008) Unprotected Drosophila melanogaster telomeres activate the spindle assembly checkpoint. Nature Genetics 40: 362–6.

Nelson AD and Shippen DE (2012) Surprises from the chromosome front: lessons from Arabidopsis on telomeres and telomerase. Cold Spring Harbor Symposia on Quantitative Biology 77: 7–15.

Nugent CI and Lundblad V (1998) The telomerase reverse transcriptase: components and regulation. Genes and Development 12: 1073–85.

Oganesian L and Karlseder J (2011) Mammalian 5′ C‐rich telomeric overhangs are a mark of recombination‐dependent telomere maintenance. Molecular Cell 42: 224–36.

O'Sullivan RJ and Almouzni G (2014) Assembly of telomeric chromatin to create ALTernative endings. Trends in Cell Biology 24: 675–85.

Palm W and de Lange T (2008) How shelterin protects mammalian telomeres. Annual Review of Genetics 42: 301–34.

Price CM , Boltz KA , Chaiken MF , et al. (2010) Evolution of CST function in telomere maintenance. Cell Cycle 9: 3157–65.

Raffa GD , Ciapponi L , Cenci G and Gatti M (2011) Terminin: a protein complex that mediates epigenetic maintenance of Drosophila telomeres. Nucleus 2: 383–91.

Raices M , Verdun RE , Compton SA , et al. (2008) C. elegans telomeres contain G‐strand and C‐strand overhangs that are bound by distinct proteins. Cell 132: 745–57.

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

Sfeir A , Kosiyatrakul ST , Hockemeyer D , et al. (2009) Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138: 90–103.

Vannier JB , Sarek G and Boulton SJ (2014) RTEL1: functions of a disease‐associated helicase. Trends in Cell Biology 24: 416–25.

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.

Mason JM , Frydrychova RC and Biessmann H (2008) Drosophila telomeres: an exception providing new insights. Bioessays 30: 25–37.

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.

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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]