Mutagenesis from a chemical perspective: nucleic acid reactions, repair, translation, and transcription.
Mutagenesis from a chemical perspective: nucleic acid reactions, repair, translation, and transcription.
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从化学角度来看诱变：核酸反应、修复、翻译和转录。
DOI：
10.1007/978-1-4613-3476-7_1
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Singer,B
中科院分区：
文献类型：
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作者：
Singer,B
简单的直接作用的烷化剂可以根据它们的诱变效率和它们的化学反应性来分类。最具致突变性的是N-亚硝基化合物，这些化合物在体外和体内优先与核酸氧反应。相比之下，烷基硫酸盐通常是较差的诱变剂，并且几乎仅与碱性氮反应。其他类型的烷化剂也显示出氧反应和致突变性之间的相关性。乙基化剂比类似的甲基化剂具有更强的氧特异性，并且在相当多的情况下，在较低的处理水平下也具有更强的致突变性。N-乙基-N-亚硝基脲、N-乙基-N' -亚硝基胍）在双链核酸中的作用顺序为：磷酸根N7-G > 02-T、06-G > N3-A > 04-T、02-C >其它N。在单链核酸中，C的02、A的N1和U、T或C的N3的反应性显著更大。这些衍生物中的某些已在体外转录或核糖体结合研究中显示错配;即，O2-烷基T、O 4-烷基T、O 6-烷基G、O2-烷基C、3-烷基C、3-烷基U或T和1-烷基A。在所有情况下，非特异性错配发生的频率很高。有证据表明，在细菌和哺乳动物细胞中存在各种类型的修复酶，它们可以在不同程度上去除N-3和N-7烷基嘌呤、O-6-烷基G、O-2-烷基T、O-烷基T和O-2-烷基C。DNA中的磷酸三酯看起来非常稳定，当碱基配对所必需的位点或导致空间位阻或Watson-Crick位点的电子屏蔽的位点发生取代时，结果是转录的不确定性而不是终止。据推测，任何或所有未修复的promutagenic损伤可以表示为在replication.Other诱变剂的化学反应和修复方面的描述包括简单的非烷基化剂，其中大部分改变碱基配对由于脱氨基或互变异构体的位移和芳香胺和多环芳烃的代谢产物。
Simple directly acting alkylating agents can be classified in terms of their mutagenic efficiency and their chemical reactivity. The most mutagenic are the N-nitroso compounds and these have a preference for reacting with nucleic acid oxygens in vitro and in vivo. In contrast, the alkyl sulfates are generally poor mutagens and react almost exclusively with base nitrogens. Other classes of alkylating agents also show correlations between oxygen reaction and mutagenicity. Ethylating agents are more oxygen-specific than the analogous methylating agent and, in a substantial number of cases, also more mutagenic at lower levels of treatment.Sites of substitution by ethyl nitroso compounds (e,g., N-ethyl-N-nitrosourea, N-ethyl-N’ -vitro-N-nitrosoguanidine) in doublestranded nucleic acids are as follows: phosphate ≫ N7-G > 02-T, 06-G > N3-A > 04-T, 02-C > other N. In single-stranded nucleic acids the reactivity of the 02of C, Nl of A, and N3 of U, T, or C is considerably greater. Certain of these derivatives have been shown in in vitro transcription or ribosome binding studies to mispair; namely, 02-alkyl T, 04-alkyl T, 06-alkyl G, 02-alkyl C, 3-alkyl C, 3-alkyl U or T, and 1-alkyl A. In all cases, nonspecif is mispairing occurs with high frequency. During in vivo replication such errors are probably relatively rare but nevertheless postulated to occur.There is evidence that various types of repair enzymes exist in bacteria and mammalian cells that can remove, to varying extents, N-3 and N-7 alkyl purines, O6-alkyl G, 02-alkyl T, 0 -alkyl T, and 02-alkyl C. Phosphotriesters in DNA appear to be very stable.When substitution occurs on a site necessary for basepairing or in a site causing steric hindrance or electronic shielding of Watson-Crick sites, the result is ambiguity in transcription rather than termination. It is hypothesized that any or all unrepaired promutagenic lesions can be expressed as errors during replication.Other mutagens described in terms of their chemical reactions and repair include simple nonalkylating agents, most of which change basepairing due to deamination or tautomeric shifts and the metabolic products of aromatic amines and polyaromatic hydrocarbons.