Tethering telomerase to telomeres increases genome instability and promotes chronological aging in yeast
2016-11
发表期刊AGING-US
ISSN1945-4589
卷号8期号:11页码:2827-2847
发表状态已发表
DOI10.18632/aging.101095
摘要Chronological aging of the yeast Saccharomyces cerevisiae is attributed to multi-faceted traits especially those involving genome instability, and has been considered to be an aging model for post-mitotic cells in higher organisms. Telomeres are the physical ends of eukaryotic chromosomes, and are essential for genome integrity and stability. It remains elusive whether dysregulated telomerase activity affects chronological aging. We employed the CDC13-EST2 fusion gene, which tethers telomerase to telomeres, to examine the effect of constitutively active telomerase on chronological lifespan (CLS). The expression of Cdc13-Est2 fusion protein resulted in overlong telomeres (2 to 4 folds longer than normal telomeres), and long telomeres were stably maintained during long-term chronological aging. Accordingly, genome instability, manifested by accumulation of extra-chromosomal rDNA circle species, age-dependent CAN1 marker-gene mutation frequency and gross chromosomal rearrangement frequency, was significantly elevated. Importantly, inactivation of Sch9, a downstream kinase of the target of rapamycin complex 1 (TORC1), suppressed both the genome instability and accelerated chronological aging mediated by CDC13-EST2 expression. Interestingly, loss of the CDC13-EST2 fusion gene in the cells with overlong telomeres restored the regular CLS. Altogether, these data suggest that constitutively active telomerase is detrimental to the maintenance of genome stability, and promotes chronological aging in yeast.
关键词chronological aging CDC13-EST2 fusion genome instability Sch9 Rif1 yeast
收录类别SCI
语种英语
资助项目Joint NSFC-ISF (Israel Science Foundation) Research Program (NSFC)[31461143003]
WOS研究方向Cell Biology ; Geriatrics & Gerontology
WOS类目Cell Biology ; Geriatrics & Gerontology
WOS记录号WOS:000390311900018
出版者IMPACT JOURNALS LLC
WOS关键词DNA END-REPLICATION ; LIFE-SPAN ; BINDING PROTEIN ; MOTHER CELLS ; LENGTH ; SENESCENCE ; CDC13 ; LONGEVITY ; RAPAMYCIN ; SCH9
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1650
专题生命科学与技术学院_特聘教授组_周金秋组
通讯作者Liu, Jun; Zhou, Jin-Qiu
作者单位
1.Chinese Acad Sci, Innovat Ctr Cell Signaling Network,Shanghai Inst, CAS Ctr Excellence Mol Cell Sci,Inst Biochem & Ce, State Key Lab Mol Biol,Univ Chinese Acad Sci, Shanghai 200031, Peoples R China
2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位生命科学与技术学院
推荐引用方式
GB/T 7714
Liu, Jun,He, Ming-Hong,Peng, Jing,et al. Tethering telomerase to telomeres increases genome instability and promotes chronological aging in yeast[J]. AGING-US,2016,8(11):2827-2847.
APA Liu, Jun.,He, Ming-Hong.,Peng, Jing.,Duan, Yi-Min.,Lu, Yi-Si.,...&Zhou, Jin-Qiu.(2016).Tethering telomerase to telomeres increases genome instability and promotes chronological aging in yeast.AGING-US,8(11),2827-2847.
MLA Liu, Jun,et al."Tethering telomerase to telomeres increases genome instability and promotes chronological aging in yeast".AGING-US 8.11(2016):2827-2847.
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