The Cohesin Ring Uses Its Hinge to Organize DNA Using Non-topological as well as Topological Mechanisms.
The Cohesin Ring Uses Its Hinge to Organize DNA Using Non-topological as well as Topological Mechanisms.
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DOI：
10.1016/j.cell.2018.04.015
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发表时间：
2018-05-31
期刊：
影响因子：
64.5
通讯作者：
Nasmyth KA
中科院分区：
文献类型：
--
作者：
Srinivasan M;Scheinost JC;Petela NJ;Gligoris TG;Wissler M;Ogushi S;Collier JE;Voulgaris M;Kurze A;Chan KL;Hu B;Costanzo V;Nasmyth KA
正如姐妹染色单体凝聚力是由姐妹DNA在粘附素环内的捕获所介导的那样，环状微染色体的共捕获与姐妹染色单体凝聚力之间存在很好的相关性。在大多数细胞中，粘附素的加载没有赋予凝聚力，它是通过捕获单个DNA来实现的。然而，带有铰链结构域的粘附素，其正电荷的管腔被中和，尽管未能捕获DNA，但仍加载并沿染色质移动。因此，粘附素以非拓扑性和拓扑性的方式与染色质结合。由于铰链突变，而不是SMC-kleisin融合，取消了捕获，DNA可能通过铰链打开进入粘附素环。Smc1/3铰链Smc1部分中三个高度保守的赖氨酸残基的突变可以取消所有的负载，而不会影响粘附素在CEN负载位置的募集或其对ATP的水解性。我们认为，加载和转位是由ATP水解循环驱动的粘附素铰链的构象变化所介导的。染色单体凝聚力是通过姐妹DNA共包裹在粘附素环内介导的，粘附素以非拓扑和拓扑方式与染色质结合，尽管三个环界面中的任何一个关闭，但粘附素都加载到染色质上。粘附素的铰链结构域对于非拓扑性和拓扑性DNA结合是至关重要的。粘附素可以选择性地与DNA结合，而不会将其包裹起来，这表明粘附素的功能是一个新的维度。
As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most cells where cohesin loads without conferring cohesion, it does so by entrapment of individual DNAs. However, cohesin with a hinge domain whose positively charged lumen is neutralized loads and moves along chromatin despite failing to entrap DNAs. Thus, cohesin engages chromatin in non-topological, as well as topological, manners. Since hinge mutations, but not Smc-kleisin fusions, abolish entrapment, DNAs may enter cohesin rings through hinge opening. Mutation of three highly conserved lysine residues inside the Smc1 moiety of Smc1/3 hinges abolishes all loading without affecting cohesin’s recruitment to CEN loading sites or its ability to hydrolyze ATP. We suggest that loading and translocation are mediated by conformational changes in cohesin’s hinge driven by cycles of ATP hydrolysis. Chromatid cohesion is mediated by co-entrapment of sister DNAs inside cohesin rings Cohesin engages chromatin in non-topological as well as topological manners Cohesin loads onto chromatin despite closure of any of the three ring interfaces. Cohesin’s hinge domain is critical for non-topological and topological DNA association. Cohesin can selectively engage DNA without entrapping it, suggesting a new dimension to cohesin function.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
16
作者：
Haering, CH;Schoffnegger, D;Löwe, J
通讯作者：
Löwe, J
DOI：
10.1093/bioinformatics/btp472
发表时间：
2009-10-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Nicol JW;Helt GA;Blanchard SG Jr;Raja A;Loraine AE
通讯作者：
Loraine AE
影响因子：
16
作者：
Bürmann F;Basfeld A;Vazquez Nunez R;Diebold-Durand ML;Wilhelm L;Gruber S
通讯作者：
Gruber S
影响因子：
16.8
作者：
Buermann, Frank;Shin, Ho-Chul;Gruber, Stephan
通讯作者：
Gruber, Stephan