SIRT6 facilitates directional telomere movement upon oxidative damage

被引:19
作者
Gao, Ying [1 ,2 ,3 ]
Tan, Jun [2 ,3 ]
Jin, Jingyi [1 ,2 ,4 ,5 ]
Ma, Hongqiang [2 ,4 ,5 ]
Chen, Xiukai [2 ,3 ]
Leger, Brittany [2 ]
Xu, Jianquan [1 ,2 ,4 ,5 ]
Spagnol, Stephen T. [6 ]
Dahl, Kris Noel [6 ,7 ]
Levine, Arthur S. [2 ,3 ]
Liu, Yang [2 ,4 ,5 ]
Lan, Li [2 ,3 ]
机构
[1] Tsinghua Univ, Sch Med, 1 Tsinghua Yuan, Beijing 100084, Peoples R China
[2] UPMC, Hillman Canc Ctr, 5117 Ctr Ave, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, 450 Technol Dr, Pittsburgh, PA 15219 USA
[4] Univ Pittsburgh, Sch Med, Dept Med, 3550 Terrace St,Suite 1218, Pittsburgh, PA 15261 USA
[5] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, 3700 OHara St,302 Benedum Hall, Pittsburgh, PA 15260 USA
[6] Carnegie Mellon Univ, Dept Chem Engn, 5000 Forbes Ave, Pittsburgh, PA 15213 USA
[7] Carnegie Mellon Univ, Dept Biomed Engn, 5000 Forbes Ave, Pittsburgh, PA 15213 USA
基金
美国国家卫生研究院;
关键词
TRICHOSTATIN-A; DNA-DAMAGE; GENOMIC INSTABILITY; DEACETYLASE; CHROMATIN; CELLS; INDUCTION; DYNAMICS; REPAIR; ISWI;
D O I
10.1038/s41598-018-23602-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:12
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