4.6 Article

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

期刊

CELLS
卷 8, 期 7, 页码 -

出版社

MDPI
DOI: 10.3390/cells8070708

关键词

telomere; ALT; DNA repair; homologous recombination; oxidative stress; ionizing radiations

资金

  1. The Grant of Excellence Departments, MIUR-Italy [ARTICOLO 1, COMMI 314-337 LEGGE 232/2016]

向作者/读者索取更多资源

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.

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