Growth conditions that increase or decrease lifespan in Saccharomyces cerevisiae lead to corresponding decreases or increases in rates of interstitial deletions and non-reciprocal translocations.
Growth conditions that increase or decrease lifespan in Saccharomyces cerevisiae lead to corresponding decreases or increases in rates of interstitial deletions and non-reciprocal translocations.
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DOI：
10.1186/s12863-016-0447-5
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发表时间：
2016-10-21
期刊：
影响因子：
2.9
通讯作者：
Maxwell PH
中科院分区：
文献类型：
--
作者：
Maxwell PH
在许多生物体中，DNA损伤、突变和染色体异常的积累与衰老有关。在不同的衰老背景下，各种形式的基因组不稳定性如何直接影响寿命仍在积极研究中。测试改变寿命的治疗是否可以改变寿命早期的突变率，这是否可以支持基因组的不稳定性，至少是衰老速度变化的部分原因。测定了两个菌株背景的酿酒酵母在几种生长条件下的突变、直接重复重组或逆转座的比率，这些生长条件缩短或延长了酵母的时间寿命。在大多数情况下，暴露在寿命缩短条件下的年轻细胞或暴露在延长寿命条件下的年轻细胞，基因组不稳定性的比率并没有持续增加。整合到染色体右臂上的CAN1基因的一个拷贝的突变率确实显示出在改变寿命的生长条件下年轻细胞的预期增加或减少。这些突变通常是由非等位基因重组事件引起的，包括非互换易位，并且使用羟基脲诱导DNA复制应激比一般的DNA损伤剂甲烷磺酸更强烈。结果与突变率的变化不一致，总体上反映了不同的生长条件对酵母寿命的影响。非等位基因重组事件与不同生长条件对寿命的影响之间的强烈相关性表明，重组率变化导致的基因组不稳定性可能直接导致衰老速度，或者寿命改变处理可能持续增加或减少DNA复制压力。这些结果进一步支持了在多个生物体中观察到的DNA复制应激与衰老之间的联系。随着年龄的增长，可能由重组事件引起的染色体异常在多个人类组织中更加普遍，进一步在酵母中的工作可能有助于确定这种观察到的机制以及染色体异常对衰老的影响。本文的在线版本(doi：10.1186/s12863-0160447-5)包含补充材料，授权用户可以使用。
Accumulation of DNA damage, mutations, and chromosomal abnormalities is associated with aging in many organisms. How directly various forms of genomic instability contribute to lifespan in different aging contexts is still under active investigation. Testing whether treatments that alter lifespan change mutation rates early during lifespan could provide support for genomic instability being at least partly responsible for changes in the rates of aging. Rates of mutations, direct repeat recombination, or retrotransposition were measured in young cell populations from two strain backgrounds of Saccharomyces cerevisiae exposed to several growth conditions that shortened or extended yeast chronological lifespan. In most cases, rates of genomic instability did not consistently increase in young cells exposed to lifespan-shortening conditions or decrease in young cells exposed to lifespan-extending conditions. The mutation rate for a copy of the CAN1 gene integrated onto the right arm of chromosome VIII did show expected increases or decreases in young cells in the lifespan-altering growth conditions. These mutations were determined to frequently result from non-allelic recombination events, including non-reciprocal translocations, and were more strongly stimulated by using hydroxyurea to induce DNA replication stress than by the general DNA-damaging agent methyl methanesulfonate. The results are not consistent with changes in mutation rates in general mediating the influence of alternative growth conditions on yeast lifespan. The strong correlation between non-allelic recombination events and the effects of the alternative growth conditions on lifespan indicates that genomic instability due to changes in recombination rates may directly contribute to the rate of aging or that lifespan-altering treatments may consistently increase or decrease DNA replication stress. These results further support the connection between DNA replication stress and aging observed in multiple organisms. Chromosomal abnormalities that likely arise from recombination events are more prevalent in multiple human tissues with increasing age, and further work in yeast could help to define mechanisms responsible for this observation and the impact of chromosomal abnormalities on aging. The online version of this article (doi:10.1186/s12863-016-0447-5) contains supplementary material, which is available to authorized users.
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影响因子：
4.5
作者：
Fabrizio P;Hoon S;Shamalnasab M;Galbani A;Wei M;Giaever G;Nislow C;Longo VD
通讯作者：
Longo VD
影响因子：
7.8
作者：
Bernardes de Jesus B;Schneeberger K;Vera E;Tejera A;Harley CB;Blasco MA
通讯作者：
Blasco MA
影响因子：
6.7
作者：
Dennis, Shannon;Sheth, Ujwal;Priess, James R.
通讯作者：
Priess, James R.
影响因子：
4.5
作者：
Garcia, Ana Maria;Calder, R. Brent;Vijg, Jan
通讯作者：
Vijg, Jan
DOI：
10.1073/pnas.88.3.936
发表时间：
1991-02-01
影响因子：
11.1
作者：
CURCIO, MJ;GARFINKEL, DJ
通讯作者：
GARFINKEL, DJ