你是否有质疑过为什么遗传了妈妈的笑容而不是爸爸的身高？来自英国利兹大学（The University of Leeds）分子与细胞生物学研究所，邓迪大学（University of Dundee）的研究人员为解开这一疑惑：自然如何将母本和父本DNA融合起来创造出独一无二的下一代？Simon Phillips教授、Stephen Carr和Jonathan Hadden博士在世界上首次获得了一种DNA双链裂解的关键酶的3维结构。这一研究成果公布在《自然》杂志上。
T7内切酶I结构的发现是通过X射线结晶学技术完成的，这种酶从一种噬菌体——这种噬菌体与病毒相似，能攻击细菌，但是其分子过程与其它生物体，比如人类的相似。
Phillips教授表示，“虽然大家都了解这种酶起着重要的作用，但是其物理结构——对于深度剖析作用过程至关重要，至今并没有观测到过，现在我们获得了这一酶的3D结构，并且观测到了其切断DNA链的那个作用点，这对于了解DNA工作的基础机制，以及病毒如何复制体内DNA来说是一个重要的突破。”
人类中，这个过程开始于父本和母本的DNA链在任意序列融合的时候，像是T7内切酶I这样的酶在这个交联过程中起着重要的作用，创造出后代独一无二的第三种序列。
但是Phillips教授也表示在这个过程之前有时也可以观测到交联，“这是一个十分重要的过程，我们下一步希望能在比噬菌体更加复杂的体系，比如酵母中检测这一过程。”
原始出处:
Nature 449, 621-624 (4 October 2007) | doi:10.1038/nature06158; Received 24 May 2007; Accepted 7 August 2007; Published online 16 September 2007
The structural basis of Holliday junction resolution by T7 endonuclease I
Jonathan M. Hadden1, Anne-Cécile Déclais2, Stephen B. Carr1, David M. J. Lilley2 & Simon E. V. Phillips1
Astbury Centre for Structural Molecular Biology, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB complex, University of Dundee, Dundee DD1 4HN, UK
Correspondence to: Simon E. V. Phillips1 Correspondence and requests for materials should be addressed to S.E.V.P. (Email: s.e.v.phillips@leeds.ac.uk).
The four-way (Holliday) DNA junction is the central intermediate in homologous recombination, a ubiquitous process that is important in DNA repair and generation of genetic diversity1. The penultimate stage of recombination requires resolution of the DNA junction into nicked-duplex species by the action of a junction-resolving enzyme, examples of which have been identified in a wide variety of organisms2. These enzymes are nucleases that are highly selective for the structure of branched DNA. The mechanism of this selectivity has, however, been unclear in the absence of structural data. Here we present the crystal structure of the junction-resolving enzyme phage T7 endonuclease I in complex with a synthetic four-way DNA junction. Although the enzyme is structure-selective, significant induced fit occurs in the interaction, with changes in the structure of both the protein and the junction. The dimeric enzyme presents two binding channels that contact the backbones of the junction's helical arms over seven nucleotides. These interactions effectively measure the relative orientations and positions of the arms of the junction, thereby ensuring that binding is selective for branched DNA that can achieve this geometry.
