Mutagenicity of N3-methyladenine: a multi-translesion polymerase affair.
Mutagenicity of N3-methyladenine: a multi-translesion polymerase affair.
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DOI：
10.1016/j.mrfmmm.2009.10.007
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发表时间：
2010-01-05
影响因子：
2.3
通讯作者：
Fronza, Gilberto
中科院分区：
文献类型：
--
作者：
Monti, Paola;Traverso, Ilaria;Casolari, Laura;Menichini, Paola;Inga, Alberto;Ottaggio, Laura;Russo, Debora;Iyer, Prema;Gold, Barry;Fronza, Gilberto
我们最近证明，Pol和Rev 1有助于减轻Me-lex的致命作用，Me-lex选择性地产生3-甲基腺嘌呤，通过易出错的病变旁路。为了确定Polη在Me-lex诱导的病变的生物学命运中的作用，在yIG 397亲本菌株及其rev 3（Pol η）衍生物中缺失RAD 30（）基因，并且用Me-lex体外损伤的质粒DNA转化的菌株。虽然RAD 30的缺失增加了Me-lex的毒性，但对致突变性的影响取决于Me-lex诱导的DNA损伤的浓度和细胞的总体TLS能力。首次测定了Mex在rad 30株中的致突变谱，并与WT株的致突变谱进行了比较。总体而言，两种突变谱没有显着差异。对突变频率的影响和Me-lex诱导的突变谱的特征提示易出错（突变频率显著降低，并且在rad 30相对于RAD 30中突变热点处AT>TA显著降低），但也提示无出错（rad 30相对于RAD 30中AT>GC显著增加）Polη依赖性病变旁路。总之，我们先前对Pol η和Rev 1突变体的研究结果，目前对Polη的研究结果，以及TLS蛋白之间已知的物理和功能相互作用，使我们提出Me-lex诱导的病变的旁路是一个多DNA聚合酶过程，当所有三种酵母TLS聚合酶都存在时，该过程最有效。
We recently demonstrated that Polζ and Rev1 contribute to alleviate the lethal effects of Me-lex, which selectively generates 3-methyladenine, by error prone lesion bypass. In order to determine the role of Polη in the biological fate of Me-lex induced lesions, the RAD30 () gene was deleted in the yIG397 parental strain and in its rev3 (Polζ) derivative, and the strains transformed with plasmid DNA damaged in vitro by Me-lex. While deletion of RAD30 increased the toxicity of Me-lex, the impact on mutagenicity varied depending on the concentration of Me-lex induced DNA damage and the overall TLS capacity of the cells. For the first time the Me-lex induced mutation spectrum in rad30 strain was determined and compared with the spectrum previously determined in WT strain. Overall, the two mutation spectra were not significantly different. The effect on mutation frequency and the features of the Me-lex induced mutation spectra were suggestive of error prone (significant decrease of mutation frequency and significant decrease of AT>TA at a mutation hotspot in rad30 vs RAD30) but also error free (significant increase of AT>GC in rad30 vs RAD30) Polη dependent bypass of lesions. In summary, our previous results with Polζ and Rev1 mutants, the present results with Polη, and the known physical and functional interactions among TLS proteins, lead us to propose that the by-pass of Me-lex induced lesions is a multi-DNA polymerases process that is mostly effective when all three yeast TLS polymerases are present.
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影响因子：
4.8
作者：
Kelly, JD;Inga, A;Fronza, G
通讯作者：
Fronza, G
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2.9
作者：
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通讯作者：
Fronza, G