MISALIGNMENT-MEDIATED DNA-SYNTHESIS ERRORS
MISALIGNMENT-MEDIATED DNA-SYNTHESIS ERRORS
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DOI：
10.1021/bi00487a001
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发表时间：
1990-09-04
期刊：
影响因子：
2.9
通讯作者：
KUNKEL, TA
中科院分区：
文献类型：
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作者：
KUNKEL, TA
修订稿于 1990 年 5 月 25 日收到（jTenetic 信息不仅可以通过用一个碱基替换另一个碱基来改变，还可以通过添加或删除一个或多个核苷酸来改变。正如碱基替换突变一样，移码 1 突变对生物体可能是有益的，也可能是有害的。因此，了解这些突变是如何产生或避免的非常重要。产生移码突变的可能机制包括异常 DNA 聚合。二十多年来，体外 DNA 合成保真度的研究主要集中在碱基取代错误上，主要是因为开发了几种敏感的方法来检测这些错误 [参见 Loeb 和 Kunkel (1982) 和 Goodman (1988)]。因此，我们对遗传物质如何以高保真度复制和维持的大部分理解都受到与基础相关的推理的影响。 错误编码。仅在过去 5 年里，研究体外 DNA 合成过程中移码保真度的检测方法才被开发出来。本综述重点关注从这些移码保真度测定中获得的信息如何影响我们对 DNA 合成过程中模板引物错位导致的诱变的理解。 DNA 合成错误的四种途径。从最简单的移码突变开始，减去一个核苷酸 错误，请考虑在图 1 所示的模板引物上进行 DNA 聚合反应期间可能会出现什么问题。在过去 20 年中，受到最多实验关注的途径始于核苷酸的错误掺入（途径 B，代表碱基取代）。当随后从错配（途径 BB）延伸以修复错误时，可能会导致碱基取代突变。本次审查的主题是其他三种途径的证据， 所有这些都使用未对齐的模板引物。例如，在适当的序列上下文中，即当错误合并时
Revised Manuscript Received May 25, 1990 (jTenetic information can be altered not only by substituting one base for another but also by adding or deleting one or more nucleotides. Just as for base-substitution mutations, frame-shift1 mutations can be either beneficial or detrimental to an organism. Thus, understanding how these are generated or avoided is important. Included among possible mechanisms for producing frame-shift mutations is aberrant DNA polymerization. For over 2 decades, studies of the fidelity of DNA synthesis in vitro have focused heavily on base-substitution errors, primarily because several sensitive methodologies were developed for their detection [for review, see Loeb and Kunkel (1982) and Goodman (1988)]. Consequently, much of our understanding of how geneticmaterial is replicated and maintained with high fidelity is flavored with the reasoning associated with base miscoding. Only within the past 5 years have assays been developed to study frame-shift fidelity during DNA synthesis in vitro. This review focuses on how infor-mation obtained from these frame-shift fidelity assays has influenced our understanding of mutagenesis resulting from template-primer misalignments during DNA synthesis. Four Pathways for DNA Synthesis Errors. Starting with the simplest frame-shift mutation, a minus-one-nucleotide error, consider what can go wrong during a DNA polymerization reaction on the template-primer shown in Figure 1. The pathway that has receivedthe most experimental attention over the past 2 decades begins with misincorporation of a nucleotide (pathway B, for Base substitution). When this is followed by extension from the mispair (pathway BB) to fix the error, a base-substitution mutation can result. The subject of this review is the evidence for the other three pathways, all of which use a misaligned template-primer. For example, in the appropriate sequence context, ie, when the misincorpo-