A Mutation in the FHA Domain of Coprinus cinereus Nbs1 Leads to Spo11-Independent Meiotic Recombination and Chromosome Segregation
A Mutation in the FHA Domain of Coprinus cinereus Nbs1 Leads to Spo11-Independent Meiotic Recombination and Chromosome Segregation
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DOI：
10.1534/g3.113.007906
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发表时间：
2013-11-01
影响因子：
2.6
通讯作者：
Zolan, Miriam E.
中科院分区：
文献类型：
--
作者：
Crown, K. Nicole;Savytskyy, Oleksandr P.;Zolan, Miriam E.
Nbs 1是Mre 11-Rad 50-Nbs 1复合物的核心成分，在细胞对DNA双链断裂（DSB）的反应中起着重要作用，但在减数分裂中的作用却知之甚少。我们使用的担子菌灰盖鬼伞检查的减数分裂的作用。我们确定了C。cinereus NBS 1基因，并证明它对应于先前称为RAD 3的互补组。一个等位基因，nbs 1 -2，在Nbs 1 FHA结构域中携带一个点突变，并具有轻度孢子活力缺陷，减数分裂I不分离频率增加，以及改变的交叉分布。nbs 1 -2菌株进入减数分裂时磷酸化H2 AX水平增加，我们假设这代表减数分裂前复制过程中形成的未修复的DSB。在nbs 1 -2中，在前期没有明显诱导Spo 11依赖性DSB。我们认为，复制依赖的DSB，由缺陷的复制叉保护和Mre 11-Rad 50-Nbs 1复合物的处理，是有能力形成减数分裂的C。cinereus，这些交叉导致高水平的忠实染色体分离。此外，虽然交换分布在nbs 1 -2中改变，但大多数交换在亚端粒区域发现，如野生型。因此，在C。当通过Spo 11非依赖性机制诱导DSB时，维持灰黑色。
Nbs1, a core component of the Mre11-Rad50-Nbs1 complex, plays an essential role in the cellular response to DNA double-strand breaks (DSBs) and poorly understood roles in meiosis. We used the basidiomycete Coprinus cinereus to examine the meiotic roles of Nbs1. We identified the C. cinereus nbs1 gene and demonstrated that it corresponds to a complementation group previously known as rad3. One allele, nbs1-2, harbors a point mutation in the Nbs1 FHA domain and has a mild spore viability defect, increased frequency of meiosis I nondisjunction, and an altered crossover distribution. The nbs1-2 strain enters meiosis with increased levels of phosphorylated H2AX, which we hypothesize represent unrepaired DSBs formed during premeiotic replication. In nbs1-2, there is no apparent induction of Spo11-dependent DSBs during prophase. We propose that replication-dependent DSBs, resulting from defective replication fork protection and processing by the Mre11-Rad50-Nbs1 complex, are competent to form meiotic crossovers in C. cinereus, and that these crossovers lead to high levels of faithful chromosome segregation. In addition, although crossover distribution is altered in nbs1-2, the majority of crossovers were found in subtelomeric regions, as in wild-type. Therefore, the location of crossovers in C. cinereus is maintained when DSBs are induced via a Spo11-independent mechanism.