The different pathways involved in meiotic recombination in mammals

虽然目前还不清楚Mnd 1基因敲除小鼠是否与Hop 2小鼠有实质性的不同，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Hop 2小鼠不同，Mnd 1小鼠具有显着比例的精母细胞核，其显示同源配对的染色体突触，修复其所有双链断裂进展至粗线期晚期，但不显示任何交叉。这些结果强烈地表明，正如已经提出的芽殖酵母，有两个主要途径（DSBR，双链断裂修复和SDSA，链置换和链退火）用于修复小鼠中的双链断裂（DSBR主要导致交叉，SDSA仅导致非交叉），并且Hop 2可以作用于两个途径。这种小鼠也可能提供关于染色体相互作用主要是如何在同源物与姐妹篇之间传递的见解，这是导致确保染色体正确分离的交叉的基本要求。 最近，我们已经证实，Hop 2只表达在那些Mnd 1敲除精母细胞，突触他们的染色体完全。 这一发现强烈表明Hop 2负责这种突触，并且由于这些显示完整突触的精母细胞已经进行到粗线期后期的阶段，此时通常会出现交叉，这一发现也表明修复已经通过SDSA发生。 我们还表明，尽管在Mnd 1敲除背景中已经揭示了Hop 2参与SDSA途径，但在野生型小鼠中Hop 2最有可能参与该途径，因为在野生型精母细胞中Hop 2蛋白是Mnd 1蛋白的2至3倍，即，存在超过形成Hop 2/Mnd 1异源二聚体所需的过量Hop 2，所述异源二聚体起刺激RecA样重组酶Rad 51和Dmc 1的作用。 最近，我们已经确定，在小鼠中有DSB独立配对的同源染色体发生DSB引入之前。 有趣的是，Spo 11的功能，II型拓扑异构酶，介绍了休息，这是独立的DSB活动似乎是重要的，这种早期同源配对。

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. Recently, we have established that in mice there is DSB-independent pairing of homologous chromosomes that occurs before DSBs are introduced. Interestingly, a function for Spo11, the type II-like topoisomerase that introduces the breaks, which is independent of its DSB activity appears to be important for this early homologous pairing.