Shortened telomeres join to DNA breaks interfering with their correct repair.
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.
Latre
Laura
L
Department of Cell Biology, Physiology, and Immunology, and Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, E-08193 Cerdanyola del Vallès, Spain.
Tusell
Laura
L
Martin
Marta
M
Miró
Rosa
R
Egozcue
Josep
J
Blasco
María A
MA
Genescà
Anna
A
D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D020223:Chromosome Painting; D002875:Chromosomes / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects; D008677:Metaphase; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011247:Pregnancy; D011839:Radiation, Ionizing; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism* / Q000528:radiation effects
D019098:Telomerase