Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease.
Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease.
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DOI：
10.1016/j.celrep.2015.02.019
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发表时间：
2015-03-10
期刊：
影响因子：
8.8
通讯作者：
Nowotny M
中科院分区：
文献类型：
--
作者：
Gaur V;Wyatt HDM;Komorowska W;Szczepanowski RH;de Sanctis D;Gorecka KM;West SC;Nowotny M
真核细胞中同源重组和DNA修复所需的SLX 1-SLX 4内切核酸酶切割多种分支DNA结构。核酸酶亚基SLX 1通过与支架蛋白SLX 4结合而被激活。目前，对SLX 1-SLX 4的结构或其作用机制知之甚少。在这里，我们通过详细描述光滑念珠菌（Cg）Slx 1单独和与Slx 4的C-末端区域组合的晶体结构来报告SLX 1-SLX 4的结构见解。Slx 1的结构揭示了GIY-YIG核酸酶和RING结构域的紧密排列，其由长α螺旋加强。Slx 1形成稳定的同源二聚体，阻断其活性位点。Slx 1-Slx 4相互作用与Slx 1同源二聚化相互排斥，表明Slx 4激活Slx 1的机制。对Slx 1核酸酶和Slx 1-Slx 4异源二聚体的结构见解Slx 1形成稳定的同源二聚体，其中活性位点被阻断Slx 1同源二聚体和与Slx 4的相互作用是互斥的Slx 1同源二聚体转化为Slx 1-Slx 4异源二聚体被认为是激活Slx 1的SLX 1-SLX 4内切核酸酶切割分支DNA结构，并在DNA复制，重组和修复中起关键作用。Gaur等人报告单独的酵母Slx 1和与Slx 4的C-末端结构域复合的结构。这些研究揭示了Slx 1的核酸酶活性的潜在调节机制。
The SLX1-SLX4 endonuclease required for homologous recombination and DNA repair in eukaryotic cells cleaves a variety of branched DNA structures. The nuclease subunit SLX1 is activated by association with a scaffolding protein SLX4. At the present time, little is known about the structure of SLX1-SLX4 or its mechanism of action. Here, we report the structural insights into SLX1-SLX4 by detailing the crystal structure of Candida glabrata (Cg) Slx1 alone and in combination with the C-terminal region of Slx4. The structure of Slx1 reveals a compact arrangement of the GIY-YIG nuclease and RING domains, which is reinforced by a long α helix. Slx1 forms a stable homodimer that blocks its active site. Slx1-Slx4 interaction is mutually exclusive with Slx1 homodimerization, suggesting a mechanism for Slx1 activation by Slx4. Structural insights into the Slx1 nuclease and Slx1-Slx4 heterodimer Slx1 forms a stable homodimer in which the active site is blocked Slx1 homodimerization and interaction with Slx4 are mutually exclusive Conversion of Slx1 homodimer to Slx1-Slx4 heterodimer is proposed to activate Slx1 The SLX1-SLX4 endonuclease cleaves branched DNA structures and has critical roles in DNA replication, recombination, and repair. Gaur et al. report structures for yeast Slx1 alone and in complex with the C-terminal domain of Slx4. These studies reveal a potential regulatory mechanism for the nuclease activity of Slx1.
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影响因子：
16
作者：
Hodskinson, Michael R. G.;Silhan, Jan;Crossan, Gerry P.;Garaycoechea, Juan I.;Mukherjee, Shivam;Johnson, Christopher M.;Schaerer, Orlando D.;Patel, Ketan J.
通讯作者：
Patel, Ketan J.
影响因子：
10.5
作者：
Fricke, WM;Brill, SJ
通讯作者：
Brill, SJ
影响因子：
9.8
作者：
Bogliolo, Massimo;Schuster, Beatrice;Surralles, Jordi
通讯作者：
Surralles, Jordi
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：
30.8
作者：
Kim, Yonghwan;Lach, Francis P.;Desetty, Rohini;Hanenberg, Helmut;Auerbach, Arleen D.;Smogorzewska, Agata
通讯作者：
Smogorzewska, Agata