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• W2038861500 endingPage "72" @default.
• W2038861500 startingPage "60" @default.
• W2038861500 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." @default.
• W2038861500 created "2016-06-24" @default.
• W2038861500 creator A5041499358 @default.
• W2038861500 creator A5050407461 @default.
• W2038861500 creator A5050906849 @default.
• W2038861500 creator A5052942047 @default.
• W2038861500 creator A5058958595 @default.
• W2038861500 date "2008-01-01" @default.
• W2038861500 modified "2023-09-25" @default.
• W2038861500 title "Telomeres: Hallmarks of radiosensitivity" @default.
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