Section of Molecular Genetics and Microbiology and Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, 78712, USA.
Mob DNA. 2012 Dec 5;3(1):21. doi: 10.1186/1759-8753-3-21.
This article traces the pioneering contributions of phage Mu to our current knowledge of how movable elements move/transpose. Mu provided the first molecular evidence of insertion elements in E. coli, postulated by McClintock to control gene activity in maize in the pre-DNA era. An early Mu-based model successfully explained all the DNA rearrangements associated with transposition, providing a blueprint for navigating the deluge of accumulating reports on transposable element activity. Amplification of the Mu genome via transposition meant that its transposition frequencies were orders of magnitude greater than any rival, so it was only natural that the first in vitro system for transposition was established for Mu. These experiments unraveled the chemistry of the phosphoryl transfer reaction of transposition, and shed light on the nucleoprotein complexes within which they occur. They hastened a similar analysis of other transposons and ushered in the structural era where many transpososomes were crystallized. While it was a lucky break that the mechanism of HIV DNA integration turned out to be similar to that of Mu, it is no accident that current drugs for HIV integrase inhibitors owe their discovery to trailblazing experiments done with Mu. Shining the light on how movable elements restructure genomes, Mu has also given of itself generously to understanding the genome.
本文追溯了噬菌体 Mu 对我们当前对可移动元件如何移动/转位的认识的开创性贡献。Mu 为 McClintock 在 DNA 时代之前提出的控制玉米中基因活性的大肠杆菌插入元件提供了第一个分子证据。一个早期基于 Mu 的模型成功地解释了所有与转位相关的 DNA 重排，为浏览大量关于转座元件活性的报告提供了蓝图。通过转位扩增 Mu 基因组意味着其转位频率比任何竞争对手都高出几个数量级，因此 Mu 自然成为第一个建立体外转位系统的转位酶。这些实验揭示了转位磷酸转移反应的化学性质，并阐明了它们发生的核蛋白复合物。它们加速了对其他转座子的类似分析，并迎来了许多转座酶体被结晶的结构时代。虽然 HIV DNA 整合的机制与 Mu 相似是一个幸运的突破，但当前用于 HIV 整合酶抑制剂的药物的发现归功于 Mu 的开创性实验并非偶然。 Mu 阐明了可移动元件如何重组基因组，也慷慨地为理解基因组做出了贡献。
