Haber James E, Ira Gregorz, Malkova Anna, Sugawara Neal
Rosenstiel Center and Department of Biology, Brandeis University, Waltham, MA 02454-9110, USA.
Philos Trans R Soc Lond B Biol Sci. 2004 Jan 29;359(1441):79-86. doi: 10.1098/rstb.2003.1367.
Since the pioneering model for homologous recombination proposed by Robin Holliday in 1964, there has been great progress in understanding how recombination occurs at a molecular level. In the budding yeast Saccharomyces cerevisiae, one can follow recombination by physically monitoring DNA after the synchronous induction of a double-strand break (DSB) in both wild-type and mutant cells. A particularly well-studied system has been the switching of yeast mating-type (MAT) genes, where a DSB can be induced synchronously by expression of the site-specific HO endonuclease. Similar studies can be performed in meiotic cells, where DSBs are created by the Spo11 nuclease. There appear to be at least two competing mechanisms of homologous recombination: a synthesis-dependent strand annealing pathway leading to noncrossovers and a two-end strand invasion mechanism leading to formation and resolution of Holliday junctions (HJs), leading to crossovers. The establishment of a modified replication fork during DSB repair links gene conversion to another important repair process, break-induced replication. Despite recent revelations, almost 40 years after Holliday's model was published, the essential ideas he proposed of strand invasion and heteroduplex DNA formation, the formation and resolution of HJs, and mismatch repair, remain the basis of our thinking.
自1964年罗宾·霍利迪提出同源重组的开创性模型以来，在理解重组如何在分子水平上发生方面已经取得了巨大进展。在芽殖酵母酿酒酵母中，可以通过在野生型和突变细胞中同步诱导双链断裂（DSB）后对DNA进行物理监测来追踪重组。一个经过充分研究的系统是酵母交配型（MAT）基因的转换，其中可以通过位点特异性HO内切核酸酶的表达同步诱导DSB。类似的研究也可以在减数分裂细胞中进行，在减数分裂细胞中，DSB由Spo11核酸酶产生。同源重组似乎至少有两种相互竞争的机制：一种是导致非交叉的合成依赖性链退火途径，另一种是导致霍利迪连接体（HJ）形成和拆分从而导致交叉的两端链侵入机制。在DSB修复过程中建立修饰的复制叉将基因转换与另一个重要的修复过程——断裂诱导复制联系起来。尽管有了最近的发现，但在霍利迪模型发表近40年后，他提出的链侵入和异源双链DNA形成、HJ的形成和拆分以及错配修复等基本观点，仍然是我们思考的基础。
