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不同源归巢内切核酸酶同裂酶I-CreI和I-MsoI对DNA靶位点的灵活识别

Flexible DNA target site recognition by divergent homing endonuclease isoschizomers I-CreI and I-MsoI.

作者信息

Chevalier Brett, Turmel Monique, Lemieux Claude, Monnat Raymond J, Stoddard Barry L

机构信息

Division of Basic Sciences, Graduate Program in Molecular and Cellular Biology, University of Washington and the Fred Hutchinson Cancer Research Center, Seattle 98109, USA.

出版信息

J Mol Biol. 2003 May 30;329(2):253-69. doi: 10.1016/s0022-2836(03)00447-9.

Abstract

Homing endonucleases are highly specific catalysts of DNA strand breaks that induce the transposition of mobile intervening sequences containing the endonuclease open reading frame. These enzymes recognize long DNA targets while tolerating individual sequence polymorphisms within those sites. Sequences of the homing endonucleases themselves diversify to a great extent after founding intron invasion events, generating highly divergent enzymes that recognize similar target sequences. Here, we visualize the mechanism of flexible DNA recognition and the pattern of structural divergence displayed by two homing endonuclease isoschizomers. We determined structures of I-CreI bound to two DNA target sites that differ at eight of 22 base-pairs, and the structure of an isoschizomer, I-MsoI, bound to a nearly identical DNA target site. This study illustrates several principles governing promiscuous base-pair recognition by DNA-binding proteins, and demonstrates that the isoschizomers display strikingly different protein/DNA contacts. The structures allow us to determine the information content at individual positions in the binding site as a function of the distribution of direct and water-mediated contacts to nucleotide bases, and provide an evolutionary snapshot of endonucleases at an early stage of divergence in their target specificity.

摘要

归巢内切酶是DNA链断裂的高度特异性催化剂,可诱导包含内切酶开放阅读框的移动间隔序列的转座。这些酶识别长DNA靶标,同时容忍这些位点内的个体序列多态性。归巢内切酶自身的序列在起始内含子入侵事件后会在很大程度上多样化,产生识别相似靶序列的高度分化的酶。在这里,我们可视化了两种归巢内切酶同裂酶所展示的灵活DNA识别机制和结构差异模式。我们确定了与22个碱基对中的8个不同的两个DNA靶位点结合的I-CreI的结构,以及与几乎相同的DNA靶位点结合的同裂酶I-MsoI的结构。这项研究阐明了DNA结合蛋白进行混杂碱基对识别的几个原则,并证明同裂酶展示出显著不同的蛋白质/DNA接触。这些结构使我们能够根据与核苷酸碱基的直接和水介导接触的分布来确定结合位点中各个位置的信息含量,并提供了内切酶在其靶标特异性分化早期阶段的进化快照。

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