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首页> 外文期刊>The FEBS journal >Structure-specific nuclease activity of RAGs is modulated by sequence, length and phase position of flanking double-stranded DNA
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Structure-specific nuclease activity of RAGs is modulated by sequence, length and phase position of flanking double-stranded DNA

机译：RAGs的结构特异性核酸酶活性受侧翼双链DNA的序列，长度和相位置的调节

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摘要

RAGs (recombination activating genes) are responsible for the generation of antigen receptor diversity through the process of combinatorial joining of different V (variable), D (diversity) and J (joining) gene segments. In addition to its physiological property, wherein RAG functions as a sequence-specific nuclease, it can also act as a structure-specific nuclease leading to genomic instability and cancer. In the present study, we investigate the factors that regulate RAG cleavage on non-B DNA structures. We find that RAG binding and cleavage on heteroduplex DNA is dependent on the length of the double-stranded flanking region. Besides, the immediate flanking double-stranded region regulates RAG activity in a sequence-dependent manner. Interestingly, the cleavage efficiency of RAGs at the heteroduplex region is influenced by the phasing of DNA. Thus, our results suggest that sequence, length and phase positions of the DNA can affect the efficiency of RAG cleavage when it acts as a structure-specific nuclease. These findings provide novel insights on the regulation of the pathological functions of RAGs.
机译：RAG（重组激活基因）通过不同V（可变），D（多样性）和J（结合）基因片段的组合结合过程，负责抗原受体多样性的产生。除了RAG的生理特性（其中RAG充当序列特异性核酸酶）外，它还可以充当结构特异性核酸酶，从而导致基因组不稳定和癌症。在本研究中，我们调查了调节非B DNA结构上RAG裂解的因素。我们发现异源双链DNA上的RAG结合和裂解取决于双链侧翼区域的长度。此外，紧邻的双链区以序列依赖性方式调节RAG活性。有趣的是，RAGs在异源双链体区域的切割效率受DNA的定相影响。因此，我们的结果表明，当DNA作为结构特异性核酸酶时，DNA的序列，长度和相位置会影响RAG裂解的效率。这些发现为RAGs病理功能的调控提供了新颖的见解。

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