Tethering telomerase to telomeres increases genome instability and promotes chronological aging in yeast

doi:10.18632/aging.101095

	Tethering telomerase to telomeres increases genome instability and promotes chronological aging in yeast
	Liu, Jun 1; He, Ming-Hong 1; Peng, Jing 1; Duan, Yi-Min 1; Lu, Yi-Si 1; Wu, Zhenfang 1; Gong, Ting 1; Li, Hong-Tao 1; Zhou, Jin-Qiu1,2
	2016-11
发表期刊	AGING-US
ISSN	1945-4589
卷号	8 期号:11 页码:2827-2847
发表状态	已发表
DOI	10.18632/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.