Human DNA ligase I completely encircles and partially unwinds nicked DNA
Human DNA ligase I completely encircles and partially unwinds nicked DNA
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DOI：
10.1038/nature03082
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发表时间：
2004-11-25
期刊：
影响因子：
64.8
通讯作者：
Ellenberger, T
中科院分区：
文献类型：
--
作者：
Pascal, JM;O'Brien, PJ;Ellenberger, T
DNA 连接酶催化的末端连接反应是所有生物体所必需的，并且是 DNA 复制、修复和重组过程的最终步骤。 DNA 连接酶 I 是三种已充分表征的哺乳动物 DNA 连接酶之一，它在 DNA 复制过程中连接冈崎片段。在此，我们报告了与带切口的 5' 腺苷酸化 DNA 中间体形成复合物的人 DNA 连接酶 I（残基 233 至 919）的晶体结构。该结构表明，酶重新定向双螺旋的路径，以暴露用于链连接反应的切口末端。它还揭示了哺乳动物连接酶的一个独特特征：DNA 结合域，允许连接酶 I 包围其 DNA 底物，稳定 DNA 的扭曲结构，并将催化核心定位在切口上。 DNA 连接酶 I 和增殖细胞核抗原滑夹的环形形状和尺寸的相似性表明存在广泛的蛋白质-蛋白质界面，可以协调冈崎片段的连接。
The end-joining reaction catalysed by DNA ligases is required by all organisms and serves as the ultimate step of DNA replication, repair and recombination processes. One of three well characterized mammalian DNA ligases, DNA ligase I, joins Okazaki fragments during DNA replication. Here we report the crystal structure of human DNA ligase I ( residues 233 to 919) in complex with a nicked, 5' adenylated DNA intermediate. The structure shows that the enzyme redirects the path of the double helix to expose the nick termini for the strand-joining reaction. It also reveals a unique feature of mammalian ligases: a DNA-binding domain that allows ligase I to encircle its DNA substrate, stabilizes the DNA in a distorted structure, and positions the catalytic core on the nick. Similarities in the toroidal shape and dimensions of DNA ligase I and the proliferating cell nuclear antigen sliding clamp are suggestive of an extensive protein-protein interface that may coordinate the joining of Okazaki fragments.