The different pathways involved in meiotic recombination in mammals

虽然目前尚不清楚Mnd1基因敲除小鼠与Hop2小鼠是否会有本质上的不同，但现在已经清楚的是，这些小鼠是哺乳动物减数分裂的遗传信息宝库。与Hop2小鼠不同，Mnd1小鼠有相当大比例的精母细胞核显示出同源的成对染色体突触，修复所有双链断裂直到晚期粗线期，但不显示任何交叉。这些结果有力地表明，正如对发芽酵母所提出的那样，有两条主要途径(DSBR，双链断裂修复和SDSA，链置换和链退火)用于修复小鼠的双链断裂(DSBR主要导致交叉，SDSA只导致非交叉)，并且Hop2可以作用于这两条途径。这只小鼠还可能提供关于染色体相互作用主要是如何在同源基因与姐妹基因之间传递的洞察力，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只在那些与染色体完全突触的Mnd1基因敲除的精母细胞中表达。这一发现强烈表明Hop2与这种突触有关，由于这些显示完全突触的精母细胞已经进入粗线期晚期，而正常情况下会出现交叉，这一发现也表明修复是通过SDSA发生的。我们还表明，尽管Hop2参与SDSA途径的研究是在Mnd1基因敲除的背景下进行的，但在野生型小鼠中，Hop2最有可能参与这一途径，因为在野生型精母细胞中，Hop2蛋白的数量是Mnd1蛋白的2到3倍，即Hop2的过剩超出了形成Hop2/Mnd1异源二聚体所需的数量，该异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.