An MCM4 mutation detected in cancer cells affects MCM4/6/7 complex formation
An MCM4 mutation detected in cancer cells affects MCM4/6/7 complex formation
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DOI：
10.1093/jb/mvw065
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发表时间：
2016-10
期刊：
影响因子：
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通讯作者：
R. Tatsumi;Y. Ishimi
中科院分区：
文献类型：
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作者：
R. Tatsumi;Y. Ishimi
在子宫内膜的人癌细胞中检测到的MCM 4突变被表征。G486 D突变位于MCM-box内，人MCM 4中486位的甘氨酸在酿酒酵母MCM 4和硫磺硫化叶菌MCM 4中是保守的。该MCM 4突变影响人MCM 4/6/7复合物的形成，因为含有突变的MCM 4蛋白的复合物是不稳定的，并且突变的MCM 4蛋白倾向于被降解。可能的是，MCM 4突变影响与MCM 7的相互作用，从而使MCM 4/6/7复合物不稳定。当突变型MCM 4在HeLa细胞中表达时，检测到具有异常核形态的细胞，这表明在突变型MCM 4存在下DNA复制受到干扰。对该保守氨基酸在MCM 4功能中的作用进行了讨论。
An MCM4 mutation detected in human cancer cells from endometrium was characterized. The mutation of G486D is located within MCM-box and the glycine at 486 in human MCM4 is conserved in Saccharomyces cerevisiae MCM4 and Sulfolobus solfataricus MCM. This MCM4 mutation affected human MCM4/6/7 complex formation, since the complex containing the mutant MCM4 protein is unstable and the mutant MCM4 protein is tend to be degraded. It is likely that the MCM4 mutation affects the interaction with MCM7 to destabilize the MCM4/6/7 complex. Cells with abnormal nuclear morphology were detected when the mutant MCM4 was expressed in HeLa cells, suggesting that DNA replication was perturbed in the presence of the mutant MCM4. Role of the conserved amino acid in MCM4 function is discussed.