Telomeres: Hallmarks of radiosensitivity

Ali Ayouaz, Christophe Raynaud, Claire Heride, Deborah Revaud, Laure Sabatier

Research output: Contribution to journalReview article

59 Citations (Scopus)

Abstract

Telomeres are the very ends of the chromosomes. They can be seen as natural double-strand breaks (DSB), specialized structures which prevent DSB repair and activation of DNA damage checkpoints. In somatic cells, attrition of telomeres occurs after each cell division until replicative senescence. In the absence of telomerase, telomeres shorten due to incomplete replication of the lagging strand at the very end of chromosome termini. Moreover, oxidative stress and accumulating reactive oxygen species (ROS) lead to an increased telomere shortening due to a less efficient repair of SSB in telomeres. The specialized structures at telomeres include proteins involved in both telomere maintenance and DNA repair. However when a telomere is damaged and has to be repaired, those proteins might fail to perform an accurate repair of the damage. This is the starting point of this article in which we first summarize the well-established relationships between DNA repair processes and maintenance of functional telomeres. We then examine how damaged telomeres would be processed, and show that irradiation alters telomere maintenance leading to possibly dramatic consequences. Our point is to suggest that those consequences are not restricted to the short term effects such as increased radiation-induced cell death. On the contrary, we postulate that the major impact of the loss of telomere integrity might occur in the long term, during multistep carcinogenesis. Its major role would be to act as an amplificator event unmasking in one single step recessive radiation-induced mutations among thousands of genes and providing cellular proliferative advantage. Moreover, the chromosomal instability generated by damaged telomeres will favour each step of the transformation from normal to fully transformed cells.

Original languageEnglish
Pages (from-to)60-72
Number of pages13
JournalBiochimie
Volume90
Issue number1
DOIs
Publication statusPublished - 1 Jan 2008

    Fingerprint

Keywords

  • Chromosome instability
  • DNA repair
  • Radiation induced carcinogenesis
  • Radiosensitivity
  • Telomere

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ayouaz, A., Raynaud, C., Heride, C., Revaud, D., & Sabatier, L. (2008). Telomeres: Hallmarks of radiosensitivity. Biochimie, 90(1), 60-72. https://doi.org/10.1016/j.biochi.2007.09.011