Dynamics in Cre-loxP site-specific recombination

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Current opinion in structural biology Pub Date : 2024-07-18 DOI:10.1016/j.sbi.2024.102878

Mark P. Foster, Matthew J. Benedek, Tyler D. Billings, Jonathan S. Montgomery

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Abstract

Cre recombinase is a phage-derived enzyme that has found utility for precise manipulation of DNA sequences. Cre recognizes and recombines pairs of loxP sequences characterized by an inverted repeat and asymmetric spacer. Cre cleaves and religates its DNA targets such that error-prone repair pathways are not required to generate intact DNA products. Major obstacles to broader applications are lack of knowledge of how Cre recognizes its targets, and how its activity is controlled. The picture emerging from high resolution methods is that the dynamic properties of both the enzyme and its DNA target are important determinants of its activity in both sequence recognition and DNA cleavage. Improved understanding of the role of dynamics in the key steps along the pathway of Cre-loxP recombination should significantly advance our ability to both redirect Cre to new sequences and to control its DNA cleavage activity in the test tube and in cells.

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Cre-loxP 位点特异性重组的动态变化

Cre 重组酶是一种源自噬菌体的酶，可用于精确操作 DNA 序列。Cre 能识别并重组以倒置重复和不对称间隔为特征的成对 loxP 序列。Cre 可裂解和重构其 DNA 目标，这样就不需要通过容易出错的修复途径来生成完整的 DNA 产物。更广泛应用的主要障碍是不了解 Cre 如何识别其靶标以及如何控制其活性。高分辨率方法得出的结论是，酶及其 DNA 靶标的动态特性是决定其序列识别和 DNA 切割活性的重要因素。进一步了解动态特性在 Cre-loxP 重组途径关键步骤中的作用，将大大提高我们在试管和细胞中将 Cre 重定向到新序列以及控制其 DNA 切裂活性的能力。

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来源期刊

Current opinion in structural biology 生物-生化与分子生物学

CiteScore

12.20

自引率

2.90%

发文量

179

审稿时长

6-12 weeks

期刊介绍： Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In COSB, we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. [...] The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance. -Folding and Binding- Nucleic acids and their protein complexes- Macromolecular Machines- Theory and Simulation- Sequences and Topology- New constructs and expression of proteins- Membranes- Engineering and Design- Carbohydrate-protein interactions and glycosylation- Biophysical and molecular biological methods- Multi-protein assemblies in signalling- Catalysis and Regulation