Clark A J, Sandler S J
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3202.
Crit Rev Microbiol. 1994;20(2):125-42. doi: 10.3109/10408419409113552.
One of the authors (AJC) acknowledges with gratitude the important role Fernando Bastarrachea played in the author's discovery that E. coli could carry out homologous genetic recombination by multiple pathways. This in turn led to the discovery of several genes, including recF, recO, and recR, whose role in recombination would not otherwise have been detected. Subsequent genetic and biochemical studies have led to a general formulation in which there are multiple nucleolytic ways to achieve a presynaptic intermediate bound to RecA protein. Postsynaptic events in the general formulation occur by means of multiple branch migration enzymes to form Holliday DNA structures and a specific nuclease to cleave them. The general formulation is built on synapsis catalyzed by RecA protein. A second RecA-independent synapsis catalyzed by RecT (and RecE?) protein is now under study and a third type independent of both RecA and RecT has apparently been discovered. How these will affect the general formulation remains to be seen. Some proteins, most prominently RecF, RecO, and RecR, have no role in the general formulation. The hypothesis is presented that these proteins act as a switch between replication and recombination by helping to convert replication to recombination intermediates. Universality of the general formulation is supported by the widespread occurrence of recA, recB, recC, and recD genes among bacteria. Recent discovery of recA-like genes in several eukaryotes further supports its universality. We have contributed additional support by sequencing a recA-like gene from an archaeal species, thus making it plausible that the mechanism of synapsis worked out for E. coli RecA protein will hold for all three organismal domains. The boundaries of the puzzle of homologous genetic recombination therefore seem complete and the pieces to the complex picture they encompass are falling into place.
其中一位作者（AJC）衷心感谢费尔南多·巴斯塔拉切亚在其发现大肠杆菌可通过多种途径进行同源基因重组过程中所发挥的重要作用。这反过来又促成了几个基因的发现，包括recF、recO和recR，否则它们在重组中的作用是不会被发现的。随后的遗传学和生物化学研究得出了一个通用的模式，即存在多种核酸分解方式来形成与RecA蛋白结合的突触前中间体。通用模式中的突触后事件是通过多种分支迁移酶形成霍利迪DNA结构以及一种特定的核酸酶来切割它们而发生的。通用模式是建立在由RecA蛋白催化的联会基础上的。目前正在研究由RecT（和RecE？）蛋白催化的第二种不依赖RecA的联会，并且显然已经发现了第三种既不依赖RecA也不依赖RecT的联会类型。它们将如何影响通用模式还有待观察。一些蛋白质，最突出的是RecF、RecO和RecR，在通用模式中没有作用。有人提出假说，这些蛋白质通过帮助将复制转化为重组中间体，从而在复制和重组之间起到开关的作用。recA、recB、recC和recD基因在细菌中的广泛存在支持了通用模式的普遍性。最近在几种真核生物中发现了recA样基因，这进一步支持了其普遍性。我们通过对一种古细菌物种的recA样基因进行测序提供了额外的支持，从而使为大肠杆菌RecA蛋白推导出来的联会机制适用于所有三个生物域成为可能。因此，同源基因重组难题的边界似乎已经完整，它们所涵盖的复杂图景的各个部分也正在各就其位。
