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首页> 外文期刊>PLoS Genetics >Differential Association of the Conserved SUMO Ligase Zip3 with Meiotic Double-Strand Break Sites Reveals Regional Variations in the Outcome of Meiotic Recombination
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Differential Association of the Conserved SUMO Ligase Zip3 with Meiotic Double-Strand Break Sites Reveals Regional Variations in the Outcome of Meiotic Recombination

机译：保守的SUMO连接酶Zip3与减数分裂双链断裂位点的差异关联揭示了减数分裂重组结果中的区域变异。

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During the first meiotic prophase, programmed DNA double-strand breaks (DSBs) are distributed non randomly at hotspots along chromosomes, to initiate recombination. In all organisms, more DSBs are formed than crossovers (CO), the repair product that creates a physical link between homologs and allows their correct segregation. It is not known whether all DSB hotspots are also CO hotspots or if the CO/DSB ratio varies with the chromosomal location. Here, we investigated the variations in the CO/DSB ratio by mapping genome-wide the binding sites of the Zip3 protein during budding yeast meiosis. We show that Zip3 associates with DSB sites that are engaged in repair by CO, and Zip3 enrichment at DSBs reflects the DSB tendency to be repaired by CO. Moreover, the relative amount of Zip3 per DSB varies with the chromosomal location, and specific chromosomal features are associated with high or low Zip3 per DSB. This work shows that DSB hotspots are not necessarily CO hotspots and suggests that different categories of DSB sites may fulfill different functions. Author Summary For sexual reproduction, meiosis is an essential step ensuring the formation of haploid gametes from diploid precursors of the germline. This reduction in the genome's content is achieved through a specialized type of division, where a single round of DNA replication is followed by two successive rounds of chromosome segregation. The first round separates the homologs. For this to faithfully occur, homologous chromosomes pair with each other and experience recombination, catalyzed by the formation of programmed double-strand breaks (DSBs). Upon their repair, a subset of DSBs will generate crossovers, which result from an intermediate that creates a physical link between homologs and allows their correct segregation by the meiotic spindle. DSBs, as well as crossovers, do not occur randomly along chromosomes but at preferential places called hotspots. To ask if all DSB hotspots also give rise to high crossover frequency, we have systematically compared the map of DSBs with that of a protein, Zip3, which we show preferentially binds to DSB sites that are being repaired with a crossover. We discovered that several DSB hotspots rarely produce crossovers, meaning that the decision to repair a DSB with a crossover can be influenced by specific chromosomal features.
机译：在第一个减数分裂前期，程序化的DNA双链断裂（DSB）非随机地分布在沿着染色体的热点上，以启动重组。在所有生物中，形成的DSB比交叉产物（CO）多，交叉产物（CO）是在同源物之间建立物理联系并允许其正确隔离的修复产物。尚不知道所有DSB热点是否也是CO热点，或者CO / DSB比率是否随染色体位置而变化。在这里，我们通过在萌芽期酵母减数分裂过程中对全基因组的Zip3蛋白结合位点作图，研究了CO / DSB比的变化。我们显示Zip3与参与CO修复的DSB位点相关联，并且DSB处的Zip3富集反映了DSB被CO修复的趋势。此外，每个DSB的Zip3相对量随染色体位置和特定染色体特征而变化与每个DSB的Zip3高低相关。这项工作表明DSB热点不一定是CO热点，并且表明不同类别的DSB站点可能具有不同的功能。作者摘要对于有性生殖，减数分裂是确保由种系的二倍体前体形成单倍体配子的重要步骤。这种基因组含量的减少是通过特殊的分裂方式实现的，在这种分裂方式中，单轮DNA复制之后是连续的两轮染色体分离。第一轮分离同源物。为使此如实发生，同源染色体彼此配对并经历重组，这是由程序化双链断裂（DSB）形成所催化的。修复后，DSB的一个子集将产生交叉，这是由中间体产生的，该中间体在同源物之间建立了物理联系，并允许它们通过减数分裂纺锤体正确隔离。 DSB和交叉不是沿着染色体随机发生，而是在称为热点的优先位置发生。为了询问是否所有DSB热点也都产生了较高的交叉频率，我们已经系统地比较了DSB与蛋白质Zip3的图谱，我们发现该图谱优先结合通过交叉修复的DSB位点。我们发现几个DSB热点很少产生交叉现象，这意味着修复带有交叉现象的DSB的决定会受到特定染色体特征的影响。

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