Formation of hMSH4-hMSH5 heterocomplex is a prerequisite for subsequent GPS2 recruitment
Formation of hMSH4-hMSH5 heterocomplex is a prerequisite for subsequent GPS2 recruitment
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DOI：
10.1016/j.dnarep.2005.07.004
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发表时间：
2006-01-05
期刊：
影响因子：
3.8
通讯作者：
Her, CT
中科院分区：
文献类型：
--
作者：
Lee, TH;Yi, W;Her, CT
越来越多的证据表明，DNA错配修复（MMR）途径的成分在错配校正范围之外发挥着多种功能，包括调节细胞对DNA损伤和同源重组的反应。由MutS同源蛋白hMSH4和hMSH5组成的杂合体被认为在减数分裂DNA修复中起重要作用，特别是在减数分裂同源重组（HR）过程中。为了更好地了解这两种人类MutS蛋白作用的机制基础，我们已经确定了g蛋白途径抑制因子2 (GPS2)（即，脱乙酰酶复合物的一个组成部分）作为hMSH4-hMSH5异复合体的相互作用蛋白伙伴。与GPS2的相互作用完全依赖于hMSH4和hMSH5之间的物理关联，因为破坏hMSH4和hMSH5之间的相互作用完全消除了GPS2的募集。我们的分析进一步表明，与GPS2的关联是通过hMSH4-hMSH5复合物和GPS2的n端区域的界面介导的。此外，这三种蛋白在人类细胞中相互作用，微阵列数据分析表明，在减数分裂开始时，这些基因的协调表达模式。总之，我们目前的研究结果表明，gps2相关的去乙酰化酶复合物可能在同源重组过程中与hMSH4-hMSH5协同作用。(C) 2005 Elsevier B.V.版权所有
Increasing evidence suggests that components of the DNA mismatch repair (MMR) pathway play multifunctional roles beyond the scope of mismatch correction, including the modulation of cellular responses to DNA damage and homologous recombination. The heterocomplex consisting of MutS homologous proteins, hMSH4 and hMSH5, is believed to play essential roles in meiotic DNA repair particularly during the process of meiotic homologous recombination (HR). In order to gain a better understanding of the mechanistic basis underlying the roles of these two human MutS proteins, we have identified G-protein pathway suppressor 2 (GPS2) (i.e., an integral component of a deacetylase complex) as an interacting protein partner specifically for the hMSH4-hMSH5 heterocomplex. The interaction with GPS2 is entirely dependent on the physical association between hMSH4 and hMSH5, as disruption of the interaction between hMSH4 and hMSH5 completely abolishes GPS2 recruitment. Our analysis further indicates that the association with GPS2 is mediated through the interface of hMSH4-hMSH5 complex and the N-terminal region of GPS2. Moreover, these three proteins interact in human cells, and analysis of microarray data suggested a coordinated expression pattern of these genes during the onset of meiosis. Together, the results of our present study suggest that the GPS2-associated deacetylase complex might function in concert with hMSH4-hMSH5 during the process of homologous recombination. (C) 2005 Elsevier B.V. All rights reserved.