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SIRT6 facilitates directional telomere movement upon oxidative damage

Oxidative damage to telomeres leads to telomere attrition and genomic instability, resulting in poor cell viability. Telomere dynamics contribute to the maintenance of telomere integrity; however, whether oxidative damage induces telomere movement and how telomere mobility is regulated remain poorly...

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Autores principales: Gao, Ying, Tan, Jun, Jin, Jingyi, Ma, Hongqiang, Chen, Xiukai, Leger, Brittany, Xu, Jianquan, Spagnol, Stephen T., Dahl, Kris Noel, Levine, Arthur S., Liu, Yang, Lan, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876328/
https://www.ncbi.nlm.nih.gov/pubmed/29599436
http://dx.doi.org/10.1038/s41598-018-23602-0
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author Gao, Ying
Tan, Jun
Jin, Jingyi
Ma, Hongqiang
Chen, Xiukai
Leger, Brittany
Xu, Jianquan
Spagnol, Stephen T.
Dahl, Kris Noel
Levine, Arthur S.
Liu, Yang
Lan, Li
author_facet Gao, Ying
Tan, Jun
Jin, Jingyi
Ma, Hongqiang
Chen, Xiukai
Leger, Brittany
Xu, Jianquan
Spagnol, Stephen T.
Dahl, Kris Noel
Levine, Arthur S.
Liu, Yang
Lan, Li
author_sort Gao, Ying
collection PubMed
description Oxidative damage to telomeres leads to telomere attrition and genomic instability, resulting in poor cell viability. Telomere dynamics contribute to the maintenance of telomere integrity; however, whether oxidative damage induces telomere movement and how telomere mobility is regulated remain poorly understood. Here, we show that oxidative damage at telomeres triggers directional telomere movement. The presence of the human Sir2 homolog, Sirtuin 6 (SIRT6) is required for oxidative damage-induced telomeric movement. SIRT6 knock out (KO) cells show neither damage-induced telomere movement nor chromatin decondensation at damaged telomeres; both are observed in wild type (WT) cells. A deacetylation mutant of SIRT6 increases damage-induced telomeric movement in SIRT6 KO cells as well as WT SIRT6. SIRT6 recruits the chromatin-remodeling protein SNF2H to damaged telomeres, which appears to promote chromatin decondensation independent of its deacetylase activity. Together, our results suggest that SIRT6 plays a role in the regulation of telomere movement upon oxidative damage, shedding new light onto the function of SIRT6 in telomere maintenance.
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spelling pubmed-58763282018-04-02 SIRT6 facilitates directional telomere movement upon oxidative damage Gao, Ying Tan, Jun Jin, Jingyi Ma, Hongqiang Chen, Xiukai Leger, Brittany Xu, Jianquan Spagnol, Stephen T. Dahl, Kris Noel Levine, Arthur S. Liu, Yang Lan, Li Sci Rep Article Oxidative damage to telomeres leads to telomere attrition and genomic instability, resulting in poor cell viability. Telomere dynamics contribute to the maintenance of telomere integrity; however, whether oxidative damage induces telomere movement and how telomere mobility is regulated remain poorly understood. Here, we show that oxidative damage at telomeres triggers directional telomere movement. The presence of the human Sir2 homolog, Sirtuin 6 (SIRT6) is required for oxidative damage-induced telomeric movement. SIRT6 knock out (KO) cells show neither damage-induced telomere movement nor chromatin decondensation at damaged telomeres; both are observed in wild type (WT) cells. A deacetylation mutant of SIRT6 increases damage-induced telomeric movement in SIRT6 KO cells as well as WT SIRT6. SIRT6 recruits the chromatin-remodeling protein SNF2H to damaged telomeres, which appears to promote chromatin decondensation independent of its deacetylase activity. Together, our results suggest that SIRT6 plays a role in the regulation of telomere movement upon oxidative damage, shedding new light onto the function of SIRT6 in telomere maintenance. Nature Publishing Group UK 2018-03-29 /pmc/articles/PMC5876328/ /pubmed/29599436 http://dx.doi.org/10.1038/s41598-018-23602-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Gao, Ying
Tan, Jun
Jin, Jingyi
Ma, Hongqiang
Chen, Xiukai
Leger, Brittany
Xu, Jianquan
Spagnol, Stephen T.
Dahl, Kris Noel
Levine, Arthur S.
Liu, Yang
Lan, Li
SIRT6 facilitates directional telomere movement upon oxidative damage
title SIRT6 facilitates directional telomere movement upon oxidative damage
title_full SIRT6 facilitates directional telomere movement upon oxidative damage
title_fullStr SIRT6 facilitates directional telomere movement upon oxidative damage
title_full_unstemmed SIRT6 facilitates directional telomere movement upon oxidative damage
title_short SIRT6 facilitates directional telomere movement upon oxidative damage
title_sort sirt6 facilitates directional telomere movement upon oxidative damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876328/
https://www.ncbi.nlm.nih.gov/pubmed/29599436
http://dx.doi.org/10.1038/s41598-018-23602-0
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