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Open AccessArticle

X-rays Activate Telomeric Homologous Recombination Mediated Repair in Primary Cells

1
Department of Science, University of Rome “ROMA TRE”, 00146 Rome, Italy
2
Department of Pharmacology & Chemical Biology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(7), 708; https://doi.org/10.3390/cells8070708
Received: 1 April 2019 / Revised: 27 June 2019 / Accepted: 6 July 2019 / Published: 12 July 2019
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Abstract

Cancer cells need to acquire telomere maintenance mechanisms in order to counteract progressive telomere shortening due to multiple rounds of replication. Most human tumors maintain their telomeres expressing telomerase whereas the remaining 15%–20% utilize the alternative lengthening of telomeres (ALT) pathway. Previous studies have demonstrated that ionizing radiations (IR) are able to modulate telomere lengths and to transiently induce some of the ALT-pathway hallmarks in normal primary fibroblasts. In the present study, we investigated the telomere length modulation kinetics, telomeric DNA damage induction, and the principal hallmarks of ALT over a period of 13 days in X-ray-exposed primary cells. Our results show that X-ray-treated cells primarily display telomere shortening and telomeric damage caused by persistent IR-induced oxidative stress. After initial telomere erosion, we observed a telomere elongation that was associated to the transient activation of a homologous recombination (HR) based mechanism, sharing several features with the ALT pathway observed in cancer cells. Data indicate that telomeric damage activates telomeric HR-mediated repair in primary cells. The characterization of HR-mediated telomere repair in normal cells may contribute to the understanding of the ALT pathway and to the identification of novel strategies in the treatment of ALT-positive cancers. View Full-Text
Keywords: telomere; ALT; DNA repair; homologous recombination; oxidative stress; ionizing radiations telomere; ALT; DNA repair; homologous recombination; oxidative stress; ionizing radiations
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De Vitis, M.; Berardinelli, F.; Coluzzi, E.; Marinaccio, J.; O’Sullivan, R.J.; Sgura, A. X-rays Activate Telomeric Homologous Recombination Mediated Repair in Primary Cells. Cells 2019, 8, 708.

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