由于核糖体RNA基因复制缺陷而改变了生命历程。

IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Genes & genetic systems Pub Date : 2023-04-18 DOI:10.1266/ggs.22-00100
Mei Hattori, Chihiro Horigome, Théo Aspert, Gilles Charvin, Takehiko Kobayashi
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引用次数: 2

摘要

基因组不稳定是衰老的主要原因。在出芽酵母酿酒酵母中,核糖体RNA基因重复序列(rDNA)的不稳定性会缩短复制寿命。在酵母中,衰老细胞中的rDNA不稳定与染色体外rDNA环(ERCs)的积累有关,ERCs滴定了维持寿命的关键因素。在哺乳动物细胞中未检测到ERC积累,其中衰老与DNA损伤有关。为了区分DNA损伤和ERC积累对衰老的影响,我们重新分析了rDNA中存在复制起始缺陷的酵母菌株,该缺陷限制了ERC的增殖。在该菌株(rARS-∆3)的老化细胞中,rDNA变得不稳定,与野生型细胞一样,而ERCs的积累明显减少。单细胞老化分析显示,rARS-∆3细胞遵循线性生存曲线,可以具有野生型的复制寿命,尽管一小部分细胞比野生型更早停止分裂。rARS-∆3细胞在最后的细胞分裂中倍增时间增加。我们的研究结果表明,rARS-∆3的衰老与哺乳动物细胞中DNA损伤的积累有关,而不是与ERC水平升高有关。因此,该菌株应该是研究erc无关老化的一个很好的模型系统。
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Changed life course upon defective replication of ribosomal RNA genes.

Genome instability is a major cause of aging. In the budding yeast Saccharomyces cerevisiae, instability of the ribosomal RNA gene repeat (rDNA) is known to shorten replicative lifespan. In yeast, rDNA instability in an aging cell is associated with accumulation of extrachromosomal rDNA circles (ERCs) which titrate factors critical for lifespan maintenance. ERC accumulation is not detected in mammalian cells, where aging is linked to DNA damage. To distinguish effects of DNA damage from those of ERC accumulation on senescence, we re-analyzed a yeast strain with a replication initiation defect in the rDNA, which limits ERC multiplication. In aging cells of this strain (rARS-∆3) rDNA became unstable, as in wild-type cells, whereas significantly fewer ERCs accumulated. Single-cell aging analysis revealed that rARS-∆3 cells follow a linear survival curve and can have a wild-type replicative lifespan, although a fraction of the cells stopped dividing earlier than wild type. The doubling time of rARS-∆3 cells appears to increase in the final cell divisions. Our results suggest that senescence in rARS-∆3 is linked to the accumulation of DNA damage as in mammalian cells, rather than to elevated ERC level. Therefore, this strain should be a good model system to study ERC-independent aging.

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来源期刊
Genes & genetic systems
Genes & genetic systems 生物-生化与分子生物学
CiteScore
1.50
自引率
0.00%
发文量
22
审稿时长
>12 weeks
期刊介绍: Genes & Genetic Systems , formerly the Japanese Journal of Genetics , is published bimonthly by the Genetics Society of Japan.
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