Introduction

AddAB enzyme is a helicase–nuclease complex that initiates recombinational repair of double-stranded DNA breaks. It catalyzes processive DNA unwinding and concomitant resection of the unwound strands, which are modulated by the recognition of a recombination hotspot called Chi in the 3′-terminated strand. Despite extensive structural, biochemical and single molecule studies, the detailed molecular mechanism of DNA unwinding by the complex and modulation by Chi sequence remains unclear.

Methods

A model of DNA unwinding by the AddAB complex and modulation by Chi recognition was presented, based on which the dynamics of AddAB complex was studied analytically.

Results

The theoretical results explain well the available experimental data on effect of DNA sequence on velocity, effect of Chi recognition on velocity, static disorder peculiar to the AddAB complex, and dynamics of pausing of wild-type and mutant AddAB complexes occurring at Chi or Chi-like sequence. Predictions were provided. Comparisons of AddAB complex with other helicase–nuclease complexes such as RecBCD and AdnAB were made.

Conclusions

The study has strong implications for the molecular mechanism of DNA unwinding by the AddAB complex. The intriguing issues are addressed of why Chi recognition is an inefficient process, how AddAB complex pauses upon recognizing Chi sequence, how the paused state transits to the translocating state, why the mutant AddAB with a stronger affinity to Chi sequence has a shorter pausing lifetime, why the pausing lifetime is sensitive to the solution temperature, and so on.

中文翻译：

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AddAB Helicase-Nuclease 模拟 DNA 解旋和 Chi 序列调制：与 AdnAB 和 RecBCD 的比较。

介绍

AddAB 酶是一种解旋酶-核酸酶复合物，可启动双链 DNA 断裂的重组修复。它催化进行性 DNA 解旋和同时切除解旋链，这些解旋链通过识别 3' 末端链中称为 Chi 的重组热点来调节。尽管进行了广泛的结构、生化和单分子研究，但复杂的 DNA 解旋和 Chi 序列调节的详细分子机制仍不清楚。

方法

提出了AddAB复合物解链DNA和Chi识别调制的模型，并在此基础上对AddAB复合物的动力学进行了分析研究。

结果

理论结果很好地解释了关于 DNA 序列对速度的影响、Chi 识别对速度的影响、AddAB 复合物特有的静态无序以及在 Chi 或 Chi- 发生的野生型和突变 AddAB 复合物的暂停动力学的可用实验数据。像序列。提供了预测。将 AddAB 复合物与其他解旋酶-核酸酶复合物（如 RecBCD 和 AdnAB）进行了比较。

结论

该研究对 AddAB 复合物解旋 DNA 的分子机制具有重要意义。有趣的问题被解决了为什么 Chi 识别是一个低效的过程，AddAB 复合物如何在识别 Chi 序列时暂停，暂停状态如何转换到易位状态，为什么对 Chi 序列具有更强亲和力的突变 AddAB 具有更短的暂停寿命，为什么暂停寿命对溶液温度很敏感，等等。