Heyer Wolf-Dietrich
Section of Microbiology and Section of Molecular and Cellular Biology, Center for Genetics and Development, University of California, Davis, Davis, CA 95616-8665, USA.
Top Curr Genet. 2007 Mar 1;17:95-133. doi: 10.1007/978-3-540-71021-9.
The biochemistry of eukaryotic homologous recombination caught fire with the discovery that Rad51 is the eukaryotic homolog of the bacterial RecA and T4 UvsX proteins; and this field is still hot. The core reaction of homologous recombination, homology search and DNA strand invasion, along with the proteins catalyzing it, are conserved throughout evolution in principle. However, the increased complexity of eukaryotic genomes and the diversity of eukaryotic cell biology pose additional challenges to the recombination machinery. It is not surprising that this increase in complexity coincided with the evolution of new recombination proteins and novel support pathways, as well as changes in the properties of those eukaryotic recombination proteins that are evidently conserved in evolution. In humans, defects in homologous recombination lead to increased cancer predisposition, underlining the importance of this pathway for genomic stability and tumor suppression. This review will focus on the mechanisms of homologous recombination in eukaryotes as elucidated by the biochemical analysis of yeast and human proteins.
随着Rad51是细菌RecA和T4 UvsX蛋白的真核同源物这一发现,真核生物同源重组的生物化学研究燃起了热潮;并且这个领域仍然很热门。同源重组的核心反应,即同源性搜索和DNA链入侵,以及催化它的蛋白质,原则上在整个进化过程中都是保守的。然而,真核生物基因组复杂性的增加和真核细胞生物学的多样性给重组机制带来了额外的挑战。毫不奇怪,这种复杂性的增加与新的重组蛋白和新的支持途径的进化同时发生,以及那些在进化中明显保守的真核生物重组蛋白的特性发生了变化。在人类中,同源重组缺陷会导致癌症易感性增加,这突出了该途径对基因组稳定性和肿瘤抑制的重要性。本综述将重点关注通过对酵母和人类蛋白质的生化分析所阐明的真核生物同源重组机制。