Substrate specificity of the MUS81-EME2 structure selective endonuclease.
Substrate specificity of the MUS81-EME2 structure selective endonuclease.
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DOI：
10.1093/nar/gkt1333
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发表时间：
2014-04
影响因子：
14.9
通讯作者：
West SC
中科院分区：
文献类型：
--
作者：
Pepe A;West SC
MUS81在停止复制分叉的重新启动、重组中间体的分解和端粒长度的维持中起着重要的细胞作用。尽管MUS81- eme1的作用已被广泛研究，但MUS81是两种人类结构选择性内切酶MUS81- eme1和MUS81- eme2的催化亚基。目前对MUS81-EME2的活性知之甚少。在这里，我们纯化了MUS81-EME2，并将其与MUS81-EME1的活性进行了比较。我们发现MUS81-EME2是一个比MUS81-EME1更活跃的内切酶，并表现出更广泛的底物特异性。与MUS81-EME1一样，MUS81-EME2可以切割3 ' -flap、复制叉和有切口的Holliday连接，并且在完整的Holliday连接中表现出有限的内切酶活性。然而，与MUS81-EME1相反，MUS81-EME2切割D-loop重组中间体，从而通过切割3 '入侵链脱离D-loop结构。此外，MUS81-EME2在MUS81-EME1无法促进的反应中作用于5 ' -flap结构以切割双臂。这些研究表明，MUS81- eme1和MUS81- eme2具有相似但不同的DNA结构选择性，这表明两种MUS81复合物在体内可能促进不同的溶核裂解反应。
MUS81 plays important cellular roles in the restart of stalled replication forks, the resolution of recombination intermediates and in telomere length maintenance. Although the actions of MUS81-EME1 have been extensively investigated, MUS81 is the catalytic subunit of two human structure-selective endonucleases, MUS81-EME1 and MUS81-EME2. Little is presently known about the activities of MUS81-EME2. Here, we have purified MUS81-EME2 and compared its activities with MUS81-EME1. We find that MUS81-EME2 is a more active endonuclease than MUS81-EME1 and exhibits broader substrate specificity. Like MUS81-EME1, MUS81-EME2 cleaves 3′-flaps, replication forks and nicked Holliday junctions, and exhibits limited endonuclease activity with intact Holliday junctions. In contrast to MUS81-EME1, however, MUS81-EME2 cuts D-loop recombination intermediates and in so doing disengages the D-loop structure by cleaving the 3′-invading strand. Additionally, MUS81-EME2 acts on 5′-flap structures to cleave off a duplex arm, in reactions that cannot be promoted by MUS81-EME1. These studies suggest that MUS81-EME1 and MUS81-EME2 exhibit similar and yet distinct DNA structure selectivity, indicating that the two MUS81 complexes may promote different nucleolytic cleavage reactions in vivo.
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SLX1和MUS81-EME1核酸酶对Holliday连接分辨率和DNA修复的合作控制。
影响因子：
16
作者：
Castor, Dennis;Nair, Nidhi;Declais, Anne-Cecile;Lachaud, Christophe;Toth, Rachel;Macartney, Thomas J.;Lilley, David M. J.;Arthur, J. Simon C.;Rouse, John
通讯作者：
Rouse, John
影响因子：
16
作者：
Jessop, Lea;Lichten, Michael
通讯作者：
Lichten, Michael
影响因子：
4.8
作者：
Ögrünç, M;Sancar, A
通讯作者：
Sancar, A
影响因子：
16
作者：
Ciccia, Alberto;Ling, Chen;West, Stephen C.
通讯作者：
West, Stephen C.
影响因子：
11.4
作者：
Abraham, J;Lemmers, B;Hakem, R
通讯作者：
Hakem, R