Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Crit Rev Biochem Mol Biol. 2010 Feb;45(1):50-69. doi: 10.3109/10409230903505596.
DNA rearrangements are important in genome function and evolution. Genetic material can be rearranged inadvertently during processes such as DNA repair, or can be moved in a controlled manner by enzymes specifically dedicated to the task. DNA transposases comprise one class of such enzymes. These move DNA segments known as transposons to new locations, without the need for sequence homology between transposon and target site. Several biochemically distinct pathways have evolved for DNA transposition, and genetic and biochemical studies have provided valuable insights into many of these. However, structural information on transposases - particularly with DNA substrates - has proven elusive in most cases. On the other hand, large-scale genome sequencing projects have led to an explosion in the number of annotated prokaryotic and eukaryotic mobile elements. Here, we briefly review biochemical and mechanistic aspects of DNA transposition, and propose that integrating sequence information with structural information using bioinformatics tools such as secondary structure prediction and protein threading can lead not only to an additional level of understanding but possibly also to testable hypotheses regarding transposition mechanisms. Detailed understanding of transposition pathways is a prerequisite for the long-term goal of exploiting DNA transposons as genetic tools and as a basis for genetic medical applications.
DNA 重排对于基因组功能和进化非常重要。遗传物质在 DNA 修复等过程中可能会意外地发生重排，也可以通过专门用于该任务的酶以受控的方式移动。DNA 转座酶就是这样的一种酶。这些酶将称为转座子的 DNA 片段转移到新的位置，而不需要转座子和靶位点之间的序列同源性。已经进化出几种生化上不同的 DNA 转座途径，遗传和生化研究为其中的许多途径提供了有价值的见解。然而，在大多数情况下，转座酶的结构信息——特别是与 DNA 底物相关的信息——仍然难以捉摸。另一方面，大规模的基因组测序项目导致了注释的原核和真核移动元件数量的爆炸式增长。在这里，我们简要回顾了 DNA 转座的生化和机制方面，并提出使用生物信息学工具（如二级结构预测和蛋白质穿线）将序列信息与结构信息结合起来，不仅可以提高对转座机制的理解水平，还可能提出可测试的假设。详细了解转座途径是将 DNA 转座子用作遗传工具和作为遗传医学应用基础的长期目标的前提。
