人类Mus81-Eme1作用于霍利迪连接结构的切割机制。
Cleavage mechanism of human Mus81-Eme1 acting on Holliday-junction structures.
作者信息
Taylor Ewan R, McGowan Clare H
机构信息
Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3757-62. doi: 10.1073/pnas.0710291105. Epub 2008 Feb 29.
Abstract
Recombination-mediated repair plays a central role in maintaining genomic integrity during DNA replication. The human Mus81-Eme1 endonuclease is involved in recombination repair, but the exact structures it acts on in vivo are not known. Using kinetic and enzymatic analysis of highly purified recombinant enzyme, we find that Mus81-Eme1 catalyzes coordinate bilateral cleavage of model Holliday-junction structures. Using a self-limiting, cruciform-containing substrate, we demonstrate that bilateral cleavage occurs sequentially within the lifetime of the enzyme-substrate complex. Coordinate bilateral cleavage is promoted by the highly cooperative nature of the enzyme and results in symmetrical cleavage of a cruciform structure, thus, Mus81-Eme1 can ensure coordinate, bilateral cleavage of Holliday junction-like structures.
摘要
重组介导的修复在DNA复制过程中维持基因组完整性方面发挥着核心作用。人类Mus81-Eme1核酸内切酶参与重组修复，但它在体内作用的具体结构尚不清楚。通过对高度纯化的重组酶进行动力学和酶学分析，我们发现Mus81-Eme1催化模型霍利迪连接结构的协同双边切割。使用一种自限性、含十字形的底物，我们证明双边切割在酶-底物复合物的寿命内依次发生。酶的高度协同性质促进了协同双边切割，并导致十字形结构的对称切割，因此，Mus81-Eme1可以确保霍利迪连接样结构的协同双边切割。
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