Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637
Genetics. 2018 Jun;209(2):357-366. doi: 10.1534/genetics.118.300958.
The persistence of hereditary traits over many generations testifies to the stability of the genetic material. Although the Watson-Crick structure for DNA provided a simple and elegant mechanism for replication, some elementary calculations implied that mistakes due to tautomeric shifts would introduce too many errors to permit this stability. It seemed evident that some additional mechanism(s) to correct such errors must be required. This essay traces the early development of our understanding of such mechanisms. Their key feature is the cutting out of a section of the strand of DNA in which the errors or damage resided, and its replacement by a localized synthesis using the undamaged strand as a template. To the surprise of some of the founders of molecular biology, this understanding derives in large part from studies in radiation biology, a field then considered by many to be irrelevant to studies of gene structure and function. Furthermore, genetic studies suggesting mechanisms of mismatch correction were ignored for almost a decade by biochemists unacquainted or uneasy with the power of such analysis. The collective body of results shows that the double-stranded structure of DNA is critical not only for replication but also as a scaffold for the correction of errors and the removal of damage to DNA. As additional discoveries were made, it became clear that the mechanisms for the repair of damage were involved not only in maintaining the stability of the genetic material but also in a variety of biological phenomena for increasing diversity, from genetic recombination to the immune response.
遗传特征在许多世代中的持续存在证明了遗传物质的稳定性。尽管沃森-克里克（Watson-Crick）的 DNA 结构为复制提供了一个简单而优雅的机制，但一些基本计算表明，由于互变异构移位而导致的错误会引入太多错误，从而无法保证这种稳定性。似乎显然需要一些其他机制来纠正这些错误。本文追溯了我们对这些机制的早期理解的发展。它们的关键特征是切除包含错误或损伤的 DNA 链的一部分，并用未受损的链作为模板进行局部合成来替换它。令一些分子生物学的创始人感到惊讶的是，这种理解在很大程度上源自辐射生物学的研究，当时许多人认为该领域与基因结构和功能的研究无关。此外，遗传研究表明，错配校正机制几乎被十年来不熟悉或不适应这种分析的生物化学家所忽视。大量的结果表明，DNA 的双链结构不仅对复制至关重要，而且对错误的校正和 DNA 损伤的去除也是至关重要的。随着更多的发现，修复损伤的机制不仅参与了遗传物质稳定性的维持，而且还参与了从遗传重组到免疫反应等各种增加多样性的生物学现象。
