The different pathways involved in meiotic recombination in mammals

尽管不清楚Mnd1基因敲除小鼠是否与Hop2小鼠有本质上的不同，但现在已经清楚的是，这些小鼠是哺乳动物减数分裂遗传信息的宝库。与Hop2小鼠不同，Mnd1小鼠有相当比例的精母细胞核显示同源配对的染色体突触，修复所有双链断裂的过程一直持续到粗线期晚期，但没有显示任何交叉。这些结果有力地表明，正如出芽酵母所提出的那样，小鼠双链断裂的修复有两种主要途径（DSBR，双链断裂修复和SDSA，双链位移和双链退火）（DSBR主要导致交叉，SDSA只导致非交叉），而Hop2可以作用于这两种途径。这只小鼠也可能提供关于染色体相互作用主要是如何在同系物和姐妹之间进行的见解，这是导致交叉的基本要求，确保染色体的适当分离。最近，我们已经证实Hop2只在那些Mnd1基因敲除且染色体完全连接的精母细胞中表达。这一发现有力地表明Hop2是突触形成的原因，而且由于这些显示完整突触的精母细胞已经进入了粗线期晚期，而交叉通常会出现，这一发现也表明修复是通过SDSA发生的。我们还发现，尽管在Mnd1基因敲除背景下发现了Hop2参与SDSA途径，但在野生型小鼠中，Hop2最有可能参与这一途径，因为在野生型精细胞中，Hop2蛋白的含量是Mnd1蛋白的2至3倍，也就是说，Hop2的过量超过了形成Hop2/Mnd1异源二聚体所需的量，而Hop2/Mnd1异源二聚体的功能是刺激reca样重组酶Rad51和Dmc1。

Although it was not clear that Mnd1 knockout mice would be substantially different from Hop2 mice it has now become clear that these mice are a treasure trove of genetic information about mammalian meiosis. Unlike the Hop2 mice, the Mnd1 mice have a significant proportion of spermatocyte nuclei that show homologously paired chromosome synapsis,repair all their double-strand breaks progress up to late pachytene but do not show any crossovers. These results strongly suggest that, as has been proposed for budding yeast, there are two main pathways (DSBR, Double-Strand Break Repair and SDSA, Strand Displacement and Strand-Annealing) for the repair of double-strand breaks in mice (DSBR leads to mainly crossovers and SDSA results in non-crossovers exclusively) and that Hop2 can act on both pathways. This mouse might also provide insights into how chromosome interactions are channeled primarily between homologs versus sisters, a fundamental requirement leading to the crossovers that ensure the proper segregation of chromosomes. Recently, we have confirmed that Hop2 is only expressed in those Mnd1 knockout spermatocytes that synapse their chromosomes completely. This finding strongly suggests that Hop2 is responsible for this synapsis and since these spermatocytes that show complete synapsis have proceeded to a stage late in pachytene when crossovers would have normally appeared, this finding also indicates that the repair has occurred via the SDSA. We have also shown that although the involvement of Hop2 in the SDSA pathway has been revealed in the Mnd1 knockout background, Hop2 is most likely involved in this pathway in the wild-type mouse as there is 2 to 3 times as much Hop2 protein as there is Mnd1 protein in wild-type spermatocytes, that is, there is an excess of Hop2 beyond that required to form the Hop2/Mnd1 heterodimer that functions to stimulate the RecA-like recombinases, Rad51 and Dmc1.