mre11S - a yeast mutation that blocks double-strand-break processing and permits nonhomologous synapsis in meiosis
mre11S - a yeast mutation that blocks double-strand-break processing and permits nonhomologous synapsis in meiosis
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DOI：
10.1101/gad.11.17.2272
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发表时间：
1997-09-01
影响因子：
10.5
通讯作者：
Klein, F
中科院分区：
文献类型：
--
作者：
Nairz, K;Klein, F
在减数分裂前期，自身造成的DNA双链断裂(DSB)损伤的修复导致酵母中的减数分裂重组。我们使用了一种基因筛查来具体描述在这种DSB形成后变得至关重要的细胞功能。因此，Mre11的一个新等位基因被分离出来，命名为mre11S(用于功能分离)，它允许启动但不能处理和修复减数分裂DSB，类似于特征很好的rad50S等位基因。相反，Mre11-1等位基因阻止了先前报道的减数分裂DSB的启动。Mre11S等位基因在基因5‘端发生突变，可部分补充3’端突变的mre11等位基因，当纯合时不能启动DSB。这表明Mre11蛋白是同源二聚的，并且存在单独的结构域用于DSB的启动和5‘端的切除。DSB处理所需的两个基因Rad50和Mre11对DSB的启动也是必不可少的，这一事实决定了一个模型，在该模型中需要一个双功能的启动/修复复合体来启动减数分裂重组。Mre11S核的一个子集表现为广泛的但部分不同源的突触。我们认为，mre11S中存在的未处理的DSB允许突触，但同源突触只在重组的后期阶段才能确保。
During meiotic prophase the repair of self-inflicted DNA double-strand break (DSB) damage leads to meiotic recombination in yeast. We employed a genetic screen to specifically characterize cellular functions that become essential after this DSB formation. As a result a new allele of MRE11, termed mre11S (for Separation of functions) was isolated that allows initiation but not processing and repair of meiotic DSBs similar to the well-characterized rad50S allele. In contrast, the mre11-1 allele blocks initiation of meiotic DSBs as reported previously by others. The mre11S allele, which is mutated in the 5' part of the gene, can partially complement mre11 alleles disrupted close to the 3' end that cannot initiate DSBs when homozygous. This suggests homodimerization of the Mre11 protein and the presence of separate domains for DSB initiation and 5' resection. The fact that two genes, RAD50 and MRE11, required for DSB processing are also essential for DSB initiation dictates a model in which a bifunctional initiation/repair complex is required to initiate meiotic recombination. A subset of mre11S nuclei was shown to perform extensive but partially nonhomologous synapsis. We propose that the unprocessed DSBs present in mre11S allow for synapsis, but that homologous synapsis is only ensured at a later stage of recombination.