Meiotic DNA Repair in the Nucleolus Employs a Nonhomologous End-Joining Mechanism[OPEN]
Meiotic DNA Repair in the Nucleolus Employs a Nonhomologous End-Joining Mechanism[OPEN]
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DOI：
10.1105/tpc.19.00367
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发表时间：
2019-02
期刊：
影响因子：
11.6
通讯作者：
Jason Sims;G. Copenhaver;P. Schlögelhofer
中科院分区：
文献类型：
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作者：
Jason Sims;G. Copenhaver;P. Schlögelhofer
rDNA在减数分裂期间通过NHEJ修复，同时被保护免于典型减数分裂DSB形成和同源重组。核糖体RNA基因以数百个rDNA单位串联的大阵列排列。这些高度重复的DNA元件对基因组稳定性构成风险，因为它们可以进行非等位基因交换。在减数分裂过程中，DNA双链断裂（DSB）被诱导作为产生配子的常规程序的一部分。减数分裂DSB启动同源重组（HR），随后确保遗传交换和染色体分离。在拟南芥（拟南芥），我们证明，所有的45S rDNA阵列成为转录活跃，并在减数分裂早期招募到核仁。这屏蔽了rDNA从获得典型的减数分裂染色质修饰和减数分裂粘附素，并只允许非常有限的减数分裂特异性DSB形成。rDNA阵列内的DNA损伤以RAD51独立但LIG4依赖的方式修复，建立非同源末端连接在减数分裂期间维持rDNA完整性。利用异位整合的rDNA重复序列，我们验证了我们的研究结果，并证明rDNA构成了HR难治性基因组环境。
The rDNA is repaired via NHEJ during meiosis while being protected from canonical meiotic DSB formation and homologous recombination. Ribosomal RNA genes are arranged in large arrays with hundreds of rDNA units in tandem. These highly repetitive DNA elements pose a risk to genome stability since they can undergo nonallelic exchanges. During meiosis, DNA double-strand breaks (DSBs) are induced as part of the regular program to generate gametes. Meiotic DSBs initiate homologous recombination (HR), which subsequently ensures genetic exchange and chromosome disjunction. In Arabidopsis (Arabidopsis thaliana), we demonstrate that all 45S rDNA arrays become transcriptionally active and are recruited into the nucleolus early in meiosis. This shields the rDNA from acquiring canonical meiotic chromatin modifications and meiotic cohesin and allows only very limited meiosis-specific DSB formation. DNA lesions within the rDNA arrays are repaired in an RAD51-independent but LIG4-dependent manner, establishing that nonhomologous end-joining maintains rDNA integrity during meiosis. Utilizing ectopically integrated rDNA repeats, we validate our findings and demonstrate that the rDNA constitutes an HR-refractory genome environment.