Mitotic Regulator Mis18 βInteracts with and Specifies the Centromeric Assembly of Molecular Chaperone Holliday Junction Recognition Protein (HJURP)
Mitotic Regulator Mis18 βInteracts with and Specifies the Centromeric Assembly of Molecular Chaperone Holliday Junction Recognition Protein (HJURP)
复制标题
有丝分裂调节因子 Mis18 beta 与分子伴侣霍利迪连接识别蛋白 (HJURP) 相互作用并指定着丝粒组装
DOI：
10.1074/jbc.m113.529958
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发表时间：
2014-03-21
影响因子：
4.8
通讯作者：
Yao, Xuebiao
中科院分区：
文献类型：
--
作者：
Wang, Jianyu;Liu, Xing;Yao, Xuebiao
背景：HJURP是着丝粒标记CENP-A沉积所必需的分子伴侣。结果：MIS18与HJURP的着丝粒定位结合，并指定着丝粒定位。结论：MIS18通过MIS18-HJURP-CENP-A轴调控着丝粒组装。意义：我们的发现揭示了CENP-A并入着丝粒的新机制。着丝粒是在有丝分裂过程中将父母基因组精确而平等地分离到两个子细胞中所必需的。CENP-A是一种在真核着丝粒中保守的独特的组蛋白H3变异体。CENP-A与着丝粒的组装是由G(1)期早期的Holliday连接识别蛋白(HJURP)介导的。然而，HJURP如何调控CENP-A整合到着丝粒中仍是个未知数。在这里，我们证明了人类HJURP直接与MIS18结合，MIS18是真核生物王国中保守的MIS18复合体的一个组成部分。Mis18结合的HJURP的最小区域被定位到残基437-460。通过RNA干扰耗尽Mis18显著削弱了HJURP向着丝粒的募集，表明Mis18在HJURP装载中的重要性。有趣的是，CDK1对HJURP的磷酸化减弱了其与Mis18的相互作用，这与CENP-A在着丝粒上的组装是在有丝分裂后实现的概念一致。综上所述，这些数据定义了一种新的分子机制，通过准确的Mis18-HJURP相互作用，支持CENP-A掺入着丝粒的时间调节。
Background: HJURP is a molecular chaperone essential for the deposition of the centromere marker CENP-A. Results: Mis18 binds with and specifies the centromere localization of HJURP. Conclusion: Mis18 governs centromere assembly via the Mis18-HJURP-CENP-A axis. Significance: Our finding reveals a novel mechanism underlying CENP-A incorporation into the centromere.The centromere is essential for precise and equal segregation of the parental genome into two daughter cells during mitosis. CENP-A is a unique histone H3 variant conserved in eukaryotic centromeres. The assembly of CENP-A to the centromere is mediated by Holliday junction recognition protein (HJURP) in early G(1) phase. However, it remains elusive how HJURP governs CENP-A incorporation into the centromere. Here we show that human HJURP directly binds to Mis18, a component of the Mis18 complex conserved in the eukaryotic kingdom. A minimal region of HJURP for Mis18 binding was mapped to residues 437-460. Depletion of Mis18 by RNA interference dramatically impaired HJURP recruitment to the centromere, indicating the importance of Mis18 in HJURP loading. Interestingly, phosphorylation of HJURP by CDK1 weakens its interaction with Mis18, consistent with the notion that assembly of CENP-A to the centromere is achieved after mitosis. Taken together, these data define a novel molecular mechanism underlying the temporal regulation of CENP-A incorporation into the centromere by accurate Mis18-HJURP interaction.