Cohesin mediates DNA loop extrusion by a "swing and clamp" mechanism.
Cohesin mediates DNA loop extrusion by a "swing and clamp" mechanism.
复制标题
DOI：
10.1016/j.cell.2021.09.016
复制
发表时间：
2021-10-14
期刊：
影响因子：
64.5
通讯作者：
Peters JM
中科院分区：
文献类型：
--
作者：
Bauer BW;Davidson IF;Canena D;Wutz G;Tang W;Litos G;Horn S;Hinterdorfer P;Peters JM
染色体结构维持（SMC）复合体在所有生命王国中组织基因组拓扑结构，并已被提出通过DNA环挤出来执行此功能。这个过程是如何工作的是未知的。在这里，我们已经分析了如何环挤压介导的人cohesin-NIPBL复合物，使染色质折叠间期细胞。我们已经确定了DNA结合位点和大规模的构象变化所需的环挤出，并确定了这些是如何协调的。我们的研究结果表明，DNA是易位的自发50 nm摆动的粘蛋白的铰链，这手的DNA的ATP酶头的SMC 3，在ATP的结合，DNA被夹持的NIPBL。在此过程中，NIPBL从铰链向SMC 3头部“跳船”，从而可能将自发铰链摆动与ATP依赖性DNA夹紧偶联。这些结果揭示了如何cohesin-NIPBL和可能的其他SMC复合物介导环挤出的机械原理。粘附素的DNA结合位点的鉴定和环挤出所需的运动铰链上的DNA结合位点可能通过ATP非依赖性摆动而使DNA移位ATP酶头上的DNA夹持由ATP依赖性接合循环调节NIPBL偶联ATP非依赖性和ATP依赖性DNA移位事件粘附素将DNA从一个结合位点长距离搬运到另一个结合位点，解释了SMC复合体如何在所有生命王国中折叠基因组。
Structural maintenance of chromosomes (SMC) complexes organize genome topology in all kingdoms of life and have been proposed to perform this function by DNA loop extrusion. How this process works is unknown. Here, we have analyzed how loop extrusion is mediated by human cohesin-NIPBL complexes, which enable chromatin folding in interphase cells. We have identified DNA binding sites and large-scale conformational changes that are required for loop extrusion and have determined how these are coordinated. Our results suggest that DNA is translocated by a spontaneous 50 nm-swing of cohesin’s hinge, which hands DNA over to the ATPase head of SMC3, where upon binding of ATP, DNA is clamped by NIPBL. During this process, NIPBL “jumps ship” from the hinge toward the SMC3 head and might thereby couple the spontaneous hinge swing to ATP-dependent DNA clamping. These results reveal mechanistic principles of how cohesin-NIPBL and possibly other SMC complexes mediate loop extrusion. Identification of cohesin’s DNA binding sites and movements needed for loop extrusion A DNA binding site on the hinge might translocate DNA by ATP-independent swinging DNA clamping on the ATPase heads is regulated by ATP-dependent engagement cycles NIPBL couples ATP-independent and -dependent DNA translocation events Cohesin hands DNA over long distances from one binding site to another, explaining how SMC complexes might fold genomes in all kingdoms of life.
登录
查看更多内容
DOI：
10.1126/science.aar7831
发表时间：
2018-04-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ganji M;Shaltiel IA;Bisht S;Kim E;Kalichava A;Haering CH;Dekker C
通讯作者：
Dekker C
影响因子：
7.7
作者：
Higashi TL;Pobegalov G;Tang M;Molodtsov MI;Uhlmann F
通讯作者：
Uhlmann F
DOI：
10.1083/jcb.200111002
发表时间：
2002-02-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Anderson DE;Losada A;Erickson HP;Hirano T
通讯作者：
Hirano T
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
DOI：
10.1073/pnas.92.11.4947
发表时间：
1995-05-23
影响因子：
11.1
作者：
CHEN, J;ZHENG, XF;SCHREIBER, SL
通讯作者：
SCHREIBER, SL