Hydrogen peroxide induced loss of heterozygosity correlates with replicative lifespan and mitotic asymmetry in Saccharomyces cerevisiae.
Hydrogen peroxide induced loss of heterozygosity correlates with replicative lifespan and mitotic asymmetry in Saccharomyces cerevisiae.
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作者：
Güven E;Parnell LA;Jackson ED;Parker MC;Gupta N;Rodrigues J;Qin H
酿酒酵母的细胞老化可导致基因组不稳定和有丝分裂不对称性受损。为了研究氧化应激在细胞衰老中的作用，我们研究了外源性过氧化氢对具有不同背景的酵母菌株的基因组不稳定性和有丝分裂不对称性的影响。我们用过氧化氢处理酵母细胞，并监测活性的变化和杂合性丢失（洛）的频率响应过氧化氢剂量。使用S形数学函数量化存活力和洛缺失的中间转变点。我们发现，过氧化氢依赖的基因组不稳定性的增加往往发生在活力下降之前。我们先前观察到，基因组不稳定性的升高通常滞后于时间老化过程中活力的下降。因此，外源性过氧化氢处理诱导的基因组不稳定性的发作是相反的，在时序老化过程中诱导的内源性氧化应激，关于活力的中点。这种对比表明，内源性氧化应激对基因组完整性的影响在时序老化过程中一直被抑制到死亡阶段。我们发现，外源性过氧化氢诱导的基因组不稳定性与复制寿命（RLS）显着相关，表明酵母细胞的抗氧化应激能力有助于其复制寿命。令人惊讶的是，这种领先优势与内源性有丝分裂不对称性的反向测量正相关，表明有丝分裂不对称性和细胞抵御过氧化氢诱导的氧化应激的能力之间的权衡。总的来说，我们的研究结果表明，在芽殖酵母的群体水平上，氧化应激与基因组不稳定性和有丝分裂不对称性有很强的关联。
Cellular aging in Saccharomyces cerevisiae can lead to genomic instability and impaired mitotic asymmetry. To investigate the role of oxidative stress in cellular aging, we examined the effect of exogenous hydrogen peroxide on genomic instability and mitotic asymmetry in a collection of yeast strains with diverse backgrounds. We treated yeast cells with hydrogen peroxide and monitored the changes of viability and the frequencies of loss of heterozygosity (LOH) in response to hydrogen peroxide doses. The mid-transition points of viability and LOH were quantified using sigmoid mathematical functions. We found that the increase of hydrogen peroxide dependent genomic instability often occurs before a drop in viability. We previously observed that elevation of genomic instability generally lags behind the drop in viability during chronological aging. Hence, onset of genomic instability induced by exogenous hydrogen peroxide treatment is opposite to that induced by endogenous oxidative stress during chronological aging, with regards to the midpoint of viability. This contrast argues that the effect of endogenous oxidative stress on genome integrity is well suppressed up to the dying-off phase during chronological aging. We found that the leadoff of exogenous hydrogen peroxide induced genomic instability to viability significantly correlated with replicative lifespan (RLS), indicating that yeast cells’ ability to counter oxidative stress contributes to their replicative longevity. Surprisingly, this leadoff is positively correlated with an inverse measure of endogenous mitotic asymmetry, indicating a trade-off between mitotic asymmetry and cell’s ability to fend off hydrogen peroxide induced oxidative stress. Overall, our results demonstrate strong associations of oxidative stress to genomic instability and mitotic asymmetry at the population level of budding yeast.
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影响因子：
9.2
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Higuchi, Ryo;Vevea, Jason D.;Swayne, Theresa C.;Chojnowski, Robert;Hill, Vanessa;Boldogh, Istvan R.;Pon, Liza A.
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