Transient ALT activation protects human primary cells from chromosome instability induced by low chronic oxidative stress
dc.contributor.author | Coluzzi, Elisa | en |
dc.contributor.author | Buonsante, Rossella | en |
dc.contributor.author | Leone, Stefano | en |
dc.contributor.author | Asmar, Anthony J. | en |
dc.contributor.author | Miller, Kelley L. | en |
dc.contributor.author | Cimini, Daniela | en |
dc.contributor.author | Sgura, Antonella | en |
dc.contributor.department | Biological Sciences | en |
dc.contributor.department | Fralin Life Sciences Institute | en |
dc.date.accessioned | 2019-01-09T17:29:48Z | en |
dc.date.available | 2019-01-09T17:29:48Z | en |
dc.date.issued | 2017-02-27 | en |
dc.description.abstract | Cells are often subjected to the effect of reactive oxygen species (ROS) as a result of both intracellular metabolism and exposure to exogenous factors. ROS-dependent oxidative stress can induce 8-oxodG within the GGG triplet found in the G-rich human telomeric sequence (TTAGGG), making telomeres highly susceptible to ROS-induced oxidative damage. Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes and their dysfunction is believed to affect a wide range of cellular and/or organismal processes. Acute oxidative stress was shown to affect telomere integrity, but how prolonged low level oxidative stress, which may be more physiologically relevant, affects telomeres is still poorly investigated. Here, we explored this issue by chronically exposing human primary fibroblasts to a low dose of hydrogen peroxide. We observed fluctuating changes in telomere length and fluctuations in the rates of chromosome instability phenotypes, such that when telomeres shortened, chromosome instability increased and when telomeres lengthened, chromosome instability decreased. We found that telomere length fluctuation is associated with transient activation of an alternative lengthening of telomere (ALT) pathway, but found no evidence of cell death, impaired proliferation, or cell cycle arrest, suggesting that ALT activation may prevent oxidative damage from reaching levels that threaten cell survival. | en |
dc.description.notes | We would like to thank Brent Bowden (Virginia Tech), Bin He (Virginia Tech), and Francesco Berardinelli (University Roma Tre) for technical assistance and all the members of the Cimini and Sgura labs for useful discussions and feedback. We would also like to acknowledge DAKO for generously supplying the chromosome 2 centromeric PNA probe. Work in the Cimini lab supported by HFSP grant RGY0069/2010 and NSF grants MCB-0842551 and MCB-1517506. | en |
dc.description.sponsorship | HFSP [RGY0069/2010]; NSF [MCB-0842551, MCB-1517506] | en |
dc.format.extent | 12 | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.doi | https://doi.org/10.1038/srep43309 | en |
dc.identifier.issn | 2045-2322 | en |
dc.identifier.other | 43309 | en |
dc.identifier.pmid | 28240303 | en |
dc.identifier.uri | http://hdl.handle.net/10919/86650 | en |
dc.identifier.volume | 7 | en |
dc.language.iso | en_US | en |
dc.publisher | Springer Nature | en |
dc.rights | Creative Commons Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
dc.subject | in-situ hybridization | en |
dc.subject | repeat amplification protocol | en |
dc.subject | dna-damage | en |
dc.subject | telomere maintenance | en |
dc.subject | human fibroblasts | en |
dc.subject | recombination | en |
dc.subject | mechanisms | en |
dc.subject | quantification | en |
dc.subject | accumulation | en |
dc.subject | micronucleus | en |
dc.title | Transient ALT activation protects human primary cells from chromosome instability induced by low chronic oxidative stress | en |
dc.title.serial | Scientific Reports | en |
dc.type | Article - Refereed | en |
dc.type.dcmitype | Text | en |
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