Telomere recombination accelerates cellular aging in Saccharomyces cerevisiae.
Telomere recombination accelerates cellular aging in Saccharomyces cerevisiae.
复制标题
DOI：
10.1371/journal.pgen.1000535
复制
发表时间：
2009-06
期刊：
影响因子：
4.5
通讯作者：
Zhou JQ
中科院分区：
文献类型：
--
作者：
Chen XF;Meng FL;Zhou JQ
端粒是位于真核生物染色体线性末端的核蛋白结构。端粒的完整性是细胞增殖和存活所必需的。虽然绝大多数真核生物使用端粒酶作为端粒维持的主要手段，但少数物种可以使用重组或逆转录转座子介导的维持途径。由于酿酒酵母可以使用端粒酶和重组来复制端粒，因此芽殖酵母提供了一个有用的系统，用于检查端粒酶和重组在自然选择下保存生物体或细胞的进化优势。在这项研究中，我们研究了端粒缺失，后衰老II型幸存者，采用同源重组复制他们的端粒的寿命。II型重组幸存者稳定地保持染色体的完整性，但表现出显着降低复制寿命。在端粒缺失的II型幸存者中观察到复制寿命和衰老依赖性不育结束时的细胞形态的正常模式，这表明II型幸存者以与野生型衰老细胞表型一致的方式过早衰老。II型生存者的寿命缩短延长热量限制或TOR1缺失，但不是由Fob1p失活或Sir2p过表达。有趣的是，在II型幸存者中rDNA重组减少，表明II型幸存者的过早衰老不是由染色体外rDNA环积累的增加引起的。重新引入端粒酶活性立即恢复复制寿命的II型幸存者，尽管他们的异质性端粒。这些结果表明，端粒重组加速细胞衰老的端粒酶无效II型幸存者和端粒酶可能是一个上级端粒维持途径，在维持酵母复制寿命。端粒是真核生物线性染色体末端的特化结构。端粒上简单的富含鸟嘌呤的DNA重复序列及其相关蛋白对染色体稳定性很重要。大多数真核生物都进化出一种叫做端粒酶的酶来复制端粒DNA。端粒酶通常含有蛋白质催化亚基和RNA模板亚基。少数真核生物可以利用端粒重组或反转录转座子介导的转座来完成端粒的延长。有趣的是，面包酵母酿酒酵母可以利用端粒酶和重组来复制端粒。在这项研究中，我们利用这种独特的真核生物模型系统，比较这两种机制在维持细胞功能和寿命方面的效率。端粒缺失细胞，使用重组延长端粒能够保持相对稳定的染色体，但是，他们表现出缩短复制寿命，这可能代表一种新的衰老途径。端粒酶的重新引入抑制了端粒重组，并恢复了这些细胞的复制寿命，这意味着端粒酶在调节酵母复制寿命方面比端粒重组优越上级。
Telomeres are nucleoprotein structures located at the linear ends of eukaryotic chromosomes. Telomere integrity is required for cell proliferation and survival. Although the vast majority of eukaryotic species use telomerase as a primary means for telomere maintenance, a few species can use recombination or retrotransposon-mediated maintenance pathways. Since Saccharomyces cerevisiae can use both telomerase and recombination to replicate telomeres, budding yeast provides a useful system with which to examine the evolutionary advantages of telomerase and recombination in preserving an organism or cell under natural selection. In this study, we examined the life span in telomerase-null, post-senescent type II survivors that have employed homologous recombination to replicate their telomeres. Type II recombination survivors stably maintained chromosomal integrity but exhibited a significantly reduced replicative life span. Normal patterns of cell morphology at the end of a replicative life span and aging-dependent sterility were observed in telomerase-null type II survivors, suggesting the type II survivors aged prematurely in a manner that is phenotypically consistent with that of wild-type senescent cells. The shortened life span of type II survivors was extended by calorie restriction or TOR1 deletion, but not by Fob1p inactivation or Sir2p over-expression. Intriguingly, rDNA recombination was decreased in type II survivors, indicating that the premature aging of type II survivors was not caused by an increase in extra-chromosomal rDNA circle accumulation. Reintroduction of telomerase activity immediately restored the replicative life span of type II survivors despite their heterogeneous telomeres. These results suggest that telomere recombination accelerates cellular aging in telomerase-null type II survivors and that telomerase is likely a superior telomere maintenance pathway in sustaining yeast replicative life span. Telomeres are the specialized structures at the ends of eukaryotic linear chromosomes. The simple guanine-rich DNA repeats at telomeres and their associated proteins are important for chromosome stability. Most eukaryotic species have evolved an enzyme named telomerase to replicate their telomeric DNA. Telomerase usually contains a protein catalytic subunit and a RNA template subunit. A few eukaryotic species can use either telomere recombination or retrotransposon-mediated transposition to accomplish telomere elongation. Interestingly, the baker's yeast Saccharomyces cerevisiae can use both telomerase and recombination to replicate telomeres. In this study, we utilize this unique eukaryotic model system to compare the efficiency of these two mechanisms in the maintenance of cellular function and life span. Telomerase-null cells that used recombination to elongate telomeres were able to maintain relatively stable chromosomes; however, they exhibited a shortened replicative life span which may represent a novel aging pathway. Reintroduction of telomerase inhibited telomere recombination and restored the replicative life span of these cells, implying that telomerase is superior to telomere recombination in the regulation of yeast replicative life span.
登录
查看更多内容
影响因子：
11.4
作者：
Herrera, E;Samper, E;Blasco, MA
通讯作者：
Blasco, MA
DOI：
10.1073/pnas.94.18.9768
发表时间：
1997-09-02
影响因子：
11.1
作者：
Austriaco, NR;Guarente, LP
通讯作者：
Guarente, LP
影响因子：
3.9
作者：
COHN, M;EDSTROM, JE
通讯作者：
EDSTROM, JE
影响因子：
1.6
作者：
Biessmann, H;Mason, JM
通讯作者：
Mason, JM
影响因子：
16
作者：
Defossez, PA;Prusty, R;Guarente, L
通讯作者：
Guarente, L