Cox M M
Department of Biochemistry, University of Wisconsin, Madison 53706.
Bioessays. 1993 Sep;15(9):617-23. doi: 10.1002/bies.950150908.
The multiple activities of the RecA protein in DNA metabolism have inspired over a decade of research in dozens of laboratories around the world. This effort has nevertheless failed to yield an understanding of the mechanism of several RecA protein-mediated processes, the DNA strand exchange reactions prominent among them. The major factors impeding progress are the invalid constraints placed upon the problem by attempting to understand RecA protein-mediated DNA strand exchange within the context of an inappropriate biological paradigm-namely, homologous genetic recombination as a mechanism for generating genetic diversity. In this essay I summarize genetic and biochemical data demonstrating that RecA protein evolved as the central component of a recombinational DNA repair system, with the generation of genetic diversity being a sometimes useful byproduct, and review the major in vitro activities of RecA protein from a repair perspective. While models proposed for both recombination and recombinational repair often make use of DNA strand cleavage and transfer steps that appear to be quite similar, the molecular and thermodynamic requirements of the two processes are very different. The recombinational repair function provides a much more logical and informative framework for thinking about the biochemical properties of RecA and the strand exchange reactions it facilitates.
RecA蛋白在DNA代谢中的多种活性激发了全球数十个实验室长达十多年的研究。然而,这项努力仍未能让人理解几种RecA蛋白介导的过程的机制,其中突出的是DNA链交换反应。阻碍进展的主要因素是,试图在不适当的生物学范式(即同源基因重组作为产生遗传多样性的机制)背景下理解RecA蛋白介导的DNA链交换,给这个问题施加了无效的限制。在本文中,我总结了遗传和生化数据,这些数据表明RecA蛋白作为重组DNA修复系统的核心成分进化而来,遗传多样性的产生有时是一种有用的副产品,并从修复的角度回顾了RecA蛋白的主要体外活性。虽然为重组和重组修复提出的模型通常都利用了似乎非常相似的DNA链切割和转移步骤,但这两个过程的分子和热力学要求却大不相同。重组修复功能为思考RecA的生化特性及其促进的链交换反应提供了一个更合乎逻辑和信息丰富的框架。