Nuclear Actin Polymerized by mDia2 Confines Centromere Movement during CENP-A Loading.
Nuclear Actin Polymerized by mDia2 Confines Centromere Movement during CENP-A Loading.
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DOI：
10.1016/j.isci.2018.10.031
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发表时间：
2018-11-30
期刊：
影响因子：
5.8
通讯作者：
Mao Y
中科院分区：
文献类型：
--
作者：
Liu C;Zhu R;Mao Y
着丝粒是由组蛋白H3变体着丝粒蛋白A（CENP-A）表观遗传学定义的特化染色体区域。CENP-A需要在每个细胞周期中补充，但新的CENP-A如何稳定地掺入着丝粒染色质仍不清楚。我们已经发现，一种细胞骨架蛋白，半透明的CIMDia 2，是新的CENP-A蛋白稳定掺入着丝粒核小体所必需的。在这里，我们报告说，mDia 2介导的动态和短的核肌动蛋白丝在G1细胞核的形成是必需的，以维持CENP-A水平在着丝粒。重要的是，在CENP-A加载期间，mDia 2和核肌动蛋白是受约束的着丝粒运动所必需的，并且消耗位于mDia 2上游的核肌动蛋白或MgcRacGAP，延长CENP-A加载伴侣蛋白Holliday连接识别蛋白（HJURP）的着丝粒缔合。因此，我们的研究结果表明，核肌动蛋白聚合mDia 2有助于物理限制G1着丝粒，使HJURP介导的CENP-A加载反应可以是生产性的，和着丝粒的表观遗传特性可以稳定地保持。形成蛋白mDia 2是在G1着丝粒处的核肌动蛋白聚合所需的核肌动蛋白聚合是维持着丝粒CENP-A水平所需的mDia 2和核肌动蛋白在CENP-A加载期间限制着丝粒运动核肌动蛋白和MgcRacGAP是着丝粒HJURP及时周转所需的细胞生物学;细胞生物学的功能方面;染色体组织;光学成像
Centromeres are specialized chromosomal regions epigenetically defined by the histone H3 variant centromere protein A (CENP-A). CENP-A needs to be replenished in every cell cycle, but how new CENP-A is stably incorporated into centromeric chromatin remains unclear. We have discovered that a cytoskeletal protein, diaphanous formin mDia2, is essential for the stable incorporation of new CENP-A proteins into centromeric nucleosomes. Here we report that mDia2-mediated formation of dynamic and short nuclear actin filaments in G1 nucleus is required to maintain CENP-A levels at the centromere. Importantly, mDia2 and nuclear actin are required for constrained centromere movement during CENP-A loading, and depleting nuclear actin or MgcRacGAP, which lies upstream of mDia2, extends centromeric association of the CENP-A loading chaperone Holliday junction recognition protein (HJURP). Our findings thus suggest that nuclear actin polymerized by mDia2 contributes to the physical confinement of G1 centromeres so that HJURP-mediated CENP-A loading reactions can be productive, and centromere's epigenetic identity can be stably maintained. Formin mDia2 is required for nuclear actin polymerization at G1 centromeres Nuclear actin polymerization is required to maintain centromeric CENP-A levels mDia2 and nuclear actin restrict centromere movement during CENP-A loading Nuclear actin and MgcRacGAP are required for timely turnover of centromeric HJURP Cell Biology; Functional Aspects of Cell Biology; Chromosome Organization; Optical Imaging
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Formin MDIA2独立于其肌动蛋白成核活性稳定微管。
影响因子：
7.8
作者：
Bartolini, Francesca;Moseley, James B.;Schmoranzer, Jan;Cassimeris, Lynne;Goode, Bruce L.;Gundersen, Gregg G.
通讯作者：
Gundersen, Gregg G.
影响因子：
56.9
作者：
Baarlink, Christian;Wang, Haicui;Grosse, Robert
通讯作者：
Grosse, Robert
影响因子：
7.8
作者：
Jansen, Lars E. T.;Black, Ben E.;Foltz, Daniel R.;Cleveland, Don W.
通讯作者：
Cleveland, Don W.
影响因子：
3.3
作者：
Belin BJ;Cimini BA;Blackburn EH;Mullins RD
通讯作者：
Mullins RD
DOI：
10.1083/jcb.200710058
发表时间：
2007-12-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dundr M;Ospina JK;Sung MH;John S;Upender M;Ried T;Hager GL;Matera AG
通讯作者：
Matera AG