Oxidative damage and mutagenesis in Saccharomyces cerevisiae: genetic studies of pathways affecting replication fidelity of 8-oxoguanine.
Oxidative damage and mutagenesis in Saccharomyces cerevisiae: genetic studies of pathways affecting replication fidelity of 8-oxoguanine.
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DOI：
10.1534/genetics.113.153874
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发表时间：
2013-10
期刊：
影响因子：
3.3
通讯作者：
Crouse GF
中科院分区：
文献类型：
--
作者：
Shockley AH;Doo DW;Rodriguez GP;Crouse GF
对DNA的氧化损伤对所有生物体中DNA的忠实复制构成重大威胁，因此重要的是要了解负责修复这种损伤的各种机制以及未修复损伤的后果。在这些实验中，我们利用酿酒酵母中的报告系统，该报告系统可以通过测量回复到Trp+表型来测量每种类型的碱基对突变的特异性增加。我们证明，增加氧化损伤由于缺乏超氧化物歧化酶基因，SOD 1，增加所有类型的碱基对突变和错配修复（MMR）减少一些，但不是所有类型的突变。通过分析在Ogg 1（编码8-oxoG糖基化酶）缺陷的背景下只能通过特定CG → AT颠换回复的各种菌株，我们可以研究由于已知8-oxoG碱基引起的诱变。我们表明，正如预期的那样，MMR有助于防止诱变，由于这个损坏的碱基和Pol η是重要的，它的准确复制。此外，我们发现，其准确的复制是由模板转换促进，因为无论是RAD 5或MMS 2的损失导致准确复制显着下降。我们观察到，这些ogg 1菌株在平板上长时间孵育过程中积累回复突变体，这一过程很可能是由于回复突变。
Oxidative damage to DNA constitutes a major threat to the faithful replication of DNA in all organisms and it is therefore important to understand the various mechanisms that are responsible for repair of such damage and the consequences of unrepaired damage. In these experiments, we make use of a reporter system in Saccharomyces cerevisiae that can measure the specific increase of each type of base pair mutation by measuring reversion to a Trp+ phenotype. We demonstrate that increased oxidative damage due to the absence of the superoxide dismutase gene, SOD1, increases all types of base pair mutations and that mismatch repair (MMR) reduces some, but not all, types of mutations. By analyzing various strains that can revert only via a specific CG → AT transversion in backgrounds deficient in Ogg1 (encoding an 8-oxoG glycosylase), we can study mutagenesis due to a known 8-oxoG base. We show as expected that MMR helps prevent mutagenesis due to this damaged base and that Pol η is important for its accurate replication. In addition we find that its accurate replication is facilitated by template switching, as loss of either RAD5 or MMS2 leads to a significant decrease in accurate replication. We observe that these ogg1 strains accumulate revertants during prolonged incubation on plates, in a process most likely due to retromutagenesis.
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影响因子：
3.9
作者：
Gredilla, Ricardo;Bohr, Vilhelm A.;Stevnsner, Tinna
通讯作者：
Stevnsner, Tinna
影响因子：
14.9
作者：
de Padula, M;Slezak, G;Boiteux, S
通讯作者：
Boiteux, S
影响因子：
30.8
作者：
Haracska, L;Yu, SL;Prakash, S
通讯作者：
Prakash, S
DOI：
10.1016/j.mrfmmm.2003.07.002
发表时间：
2003-10-29
影响因子：
2.3
作者：
Bjelland, S;Seeberg, E
通讯作者：
Seeberg, E
影响因子：
16
作者：
Brégeon, D;Doddridge, ZA;Doetsch, PW
通讯作者：
Doetsch, PW