Shortened telomeres join to DNA breaks interfering with their correct repair

Laura Latre, Laura Tusell, Marta Martin, Rosa Miró, Josep Egozcue, María A. Blasco, Anna Genescà

Research output: Contribution to journalArticleResearchpeer-review

58 Citations (Scopus)

Abstract

Telomeres cap chromosome ends, avoiding end-to-end fusions and subsequent chromosome instability. Telomeric functions and DNA repair pathways are closely related. Telomere dysfunction has been shown to result in hypersensitivity to ionizing radiation. In this study, we have used the telomerase knockout model to investigate how telomere shortening influences the correct repair of broken chromosomes. We show that the correct repair of double-strand breaks is impaired in telomerase knockout mice. The chromosomes with shortened telomeres fuse to radiation-induced breaks, interfering with the correct rejoining of the broken ends. This type of fusion is responsible for the increased chromosome instability observed in this mouse model, after exposure to ionizing radiation. Our finding may be important for understanding the increased radiation sensitivity associated with age in humans, as well as for comprehending the interindividual differences to the cytotoxic effects of radiation therapy in cancer patients. © 2003 Elsevier Science (USA). All rights reserved.
Original languageEnglish
Pages (from-to)282-288
JournalExperimental Cell Research
Volume287
DOIs
Publication statusPublished - 15 Jul 2003

Keywords

  • Chromosomal aberrations
  • DNA repair
  • End joining
  • Ionizing radiation
  • Radiosensitivity
  • Telomerase knockouts
  • Telomere

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