An MCM4 mutation detected in cancer cells affects MCM4/6/7 complex formation

R. Tatsumi, Y. Ishimi
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引用次数: 10

Abstract

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.
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在癌细胞中检测到的MCM4突变影响MCM4/6/7复合物的形成
在人子宫内膜癌细胞中检测到一种MCM4突变。G486D突变位于MCM-box内,人类MCM4中486位甘氨酸在酿酒酵母MCM4和硫酸根MCM中保守。这个MCM4突变影响了人类MCM4/6/7复合物的形成,因为含有突变MCM4蛋白的复合物是不稳定的,并且突变MCM4蛋白容易被降解。MCM4突变可能会影响与MCM7的相互作用,从而破坏MCM4/6/7复合物的稳定性。当突变体MCM4在HeLa细胞中表达时,检测到细胞核形态异常的细胞,这表明突变体MCM4存在时DNA复制受到干扰。讨论了保守氨基酸在MCM4功能中的作用。
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