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The telomerase cycle: normal and pathological aspects

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Abstract

Telomeres are nucleoprotein complexes that cap the end of eukaryotic chromosomes and are essential for their function and stability. Telomerase, a reverse transcriptase that extends the single-stranded G-rich 3′ protruding ends of chromosomes, stabilizes telomere length in germ line cells and regenerative tissues as well as in tumor cells. In the absence of telomerase telomeres shorten with cell division, a process able to trigger cell growth arrest. When telomerase is present in the cell, its activity is tightly regulated at its site of action by factors specifically bound to the telomeric DNA. Recent data indicate that telomeres reorganize during the cell cycle. This review summarizes our current knowledge on how telomeres are dynamically organized and remodeled during cell cycle and stress response, pointing out the conservation and the difference between yeast and human. We then focus on the cellular consequences of telomere modifications in normal and cancer cells. This leads to a discussion of the different roles, seemingly contradictory, of telomeres and telomerase during the initiation and the progression of a cancer

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Abbreviations

ALT :

Alternative lengthening of telomere

APB :

ALT-associated promyelocytic leukemia bodies

DNA-PK :

DNA-dependent protein kinase

DSB :

Double strand break

HR :

Homologous recombination

MRN :

MRE11/RAD50/NBS

NBS :

Nijmegen breakage syndrome protein

NHEJ :

Nonhomologous end-joining

PARP :

Poly(ADP-ribose) polymerase

PKcs :

Protein kinase catalytic subunit

Rap :

Repressor/activator protein

RPA :

Replication protein A

TRF :

Telomeric repeat binding factor

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Acknowledgements

Work in the laboratory of E.G. is supported by La Ligue Nationale contre le Cancer. M.B. is supported by a training grant from the EC. Work in the laboratory of V.G. was supported by l’Association pour la Recherche sur le Cancer and by le Ministère de la Recherche et des Nouvelles Technologies.

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  1. Laboratoire de Biologie Moleculaire de la Cellule, l’Ecole Normale de Lyon, CNRS UMR5161, INRA U1237, IFR12846 Allée d’Italie, 69364, Lyon cedex 07, France

    Michele Brunori & Eric Gilson

  2. Laboratoire d’Ingénierie des Systèmes Macromoléculaires et Institut de Biologie Structurale et Microbiologie, CNRS, 31 chemin Joseph Aiguier, 13402, Marseille cedex 20, France

    Pierre Luciano & Vincent Géli

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  1. Michele Brunori
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Correspondence to Vincent Géli.

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Brunori, M., Luciano, P., Gilson, E. et al. The telomerase cycle: normal and pathological aspects. J Mol Med 83, 244–257 (2005). https://doi.org/10.1007/s00109-004-0616-2

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