Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding.
Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding.
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DOI：
10.1038/s41467-023-41596-w
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发表时间：
2023-09-22
影响因子：
16.6
通讯作者：
Hu, Bin
中科院分区：
文献类型：
--
作者：
Kaushik, Aditi;Than, Thane;Petela, Naomi J.;Voulgaris, Menelaos;Percival, Charlotte;Daniels, Peter;Rafferty, John B.;Nasmyth, Kim A.;Hu, Bin
环状黏连蛋白复合物在姐妹染色单体黏连、DNA修复和基因转录中起关键作用。粘附素向染色体的加载需要加载器Scc 2，并受ATP调节。这一过程受到Smc 3乙酰化的阻碍。然而，这种抑制的分子机制仍然是神秘的。在这里，使用酿酒酵母作为一个模型系统，我们确定了一种新的配置Scc 2与预先从事的粘附素，并揭示动态构象的粘附素/Scc 2复合物在加载反应。我们证明，Smc 3乙酰化通过损害Scc 2与Smc 3头部的相互作用来阻断Scc 2与预先参与的粘附素的关联。最后，我们表明，ATP结合诱导cohesin/Scc 2复合物通过促进Scc 2和Smc 3卷曲螺旋之间的相互作用来夹紧DNA。我们的研究结果阐明了动态重构的cohesin/Scc 2复合物在加载过程中，并表明如何Smc 3乙酰化和ATP调节这一过程。粘附素在DNA上的加载是一个高度动态的过程。在这里，作者发现Smc 3乙酰化通过阻止Scc 2与Smc 3相互作用来阻断Scc 2/cohesin复合物的重构，并且ATP结合通过促进Scc 2/Smc 3卷曲螺旋相互作用来调节DNA夹紧步骤。
The ring-shaped cohesin complex is a key player in sister chromatid cohesion, DNA repair, and gene transcription. The loading of cohesin to chromosomes requires the loader Scc2 and is regulated by ATP. This process is hindered by Smc3 acetylation. However, the molecular mechanism underlying this inhibition remains mysterious. Here, using Saccharomyces cerevisiae as a model system, we identify a novel configuration of Scc2 with pre-engaged cohesin and reveal dynamic conformations of the cohesin/Scc2 complex in the loading reaction. We demonstrate that Smc3 acetylation blocks the association of Scc2 with pre-engaged cohesin by impairing the interaction of Scc2 with Smc3’s head. Lastly, we show that ATP binding induces the cohesin/Scc2 complex to clamp DNA by promoting the interaction between Scc2 and Smc3 coiled coil. Our results illuminate a dynamic reconfiguration of the cohesin/Scc2 complex during loading and indicate how Smc3 acetylation and ATP regulate this process. Cohesin loading on DNA is a highly dynamic process. Here the authors find that Smc3 acetylation blocks the reconfiguration of the Scc2/cohesin complex by preventing Scc2 from interacting with Smc3, and that ATP binding regulates the DNA clamping step by promoting the Scc2/Smc3 coiled-coil interaction.
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影响因子：
16.8
作者：
Bastie, Nathalie;Chapard, Christophe;Koszul, Romain
通讯作者：
Koszul, Romain
影响因子：
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Peters JM
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Beckouët F;Hu B;Roig MB;Sutani T;Komata M;Uluocak P;Katis VL;Shirahige K;Nasmyth K
通讯作者：
Nasmyth K
影响因子：
16
作者：
Haering, CH;Löwe, J;Nasmyth, K
通讯作者：
Nasmyth, K