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首页> 外文会议>Pacific Symposium on Biocomputing(PSB); 20050104-08; Hawaii,HI(US) >FROM CONTEXT-DEPENDENCE OF MUTATIONS TO MOLECULAR MECHANISMS OF MUTAGENESIS
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FROM CONTEXT-DEPENDENCE OF MUTATIONS TO MOLECULAR MECHANISMS OF MUTAGENESIS

机译：从突变的背景依赖性到诱变的分子机制

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摘要

Mutation frequencies vary significantly along nucleotide sequences such that mutations often concentrate at certain positions called hotspots. Mutation hotspots in DNA reflect intrinsic properties of the mutation process, such as sequence specificity, that manifests itself at the level of interaction between mutagens, DNA, and the action of the repair and replication machineries. The nucleotide sequence context of mutational hotspots is a fingerprint of interactions between DNA and repair/replication/modification enzymes, and the analysis of hotspot context provides evidence of such interactions. The hotspots might also reflect structural and functional features of the respective DNA sequences and provide information about natural selection. We discuss analysis of 8-oxoguanine-induced mutations in pro- and eukaryotic genes, polymorphic positions in the human mitochondrial DNA and mutations in the HIV-1 retrovirus. Comparative analysis of 8-oxoguanine-induced mutations and spontaneous mutation spectra suggested that a substantial fraction of spontaneous A·T→C·T mutations is caused by 8-oxoGTP in nucleotide pools. In the case of human mitochondrial DNA, significant differences between molecular mechanisms of mutations in hypervariable segments and coding part of DNA were detected. Analysis of mutations in the HIV-1 retrovirus suggested a complex interplay between molecular mechanisms of mutagenesis and natural selection.
机译：突变频率沿核苷酸序列变化很大，因此突变通常集中在称为热点的某些位置。 DNA中的突变热点反映了突变过程的内在特性，例如序列特异性，这在诱变剂，DNA与修复和复制机制的相互作用水平上表现出来。突变热点的核苷酸序列背景是DNA与修复/复制/修饰酶之间相互作用的指纹，并且热点背景的分析提供了这种相互作用的证据。热点还可能反映相应DNA序列的结构和功能特征，并提供有关自然选择的信息。我们讨论前亲和真核基因中8-氧鸟嘌呤诱导的突变，人线粒体DNA的多态性位置以及HIV-1逆转录病毒的突变的分析。对8-氧鸟嘌呤诱导的突变和自发突变谱的比较分析表明，自发的A·T→C·T突变的很大一部分是由核苷酸库中的8-oxoGTP引起的。在人类线粒体DNA的情况下，检测到高变段突变的分子机制与DNA的编码部分之间存在显着差异。对HIV-1逆转录病毒突变的分析表明，诱变的分子机制与自然选择之间存在复杂的相互作用。

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