MCM7是DNA解旋酶MCMs亚基之一，在DNA复制起始过程中发挥重要作用，有研究提示MCM7具有不依赖于MCMs的功能，我们前期研究发现MCM7具有提高端粒酶活性的作用, 初步结果表明MCM7能结合端粒酶催化亚基hTERT。为了阐明MCM7调控端粒酶活性的分子机制，我们拟开展以下几个方面的研究：（1）通过GST pulldown等方法确定MCM7与端粒酶hTERT的结合位点/结构域；（2）利用点突变和免疫共沉淀/免疫荧光等方法分析MCM7的磷酸化修饰是否影响其与hTERT的结合；探究MCM7是否影响hTERT与端粒酶RNA（hTR）的结合以及hTERT在细胞内的定位和稳定性；（3）建立MCM7及其功能位点突变体的表达细胞系，通过小鼠成瘤模型，分析MCM7是否通过上调hTERT活性而促进细胞成瘤性；（4）通过分析临床样本，明确MCM7蛋白水平与hTERT活性以及患者预后的相关性。

MCM7 is a subunit of MCM2-7 complex which plays an important role in the initiation of DNA replication as a DNA helicase during cell division. However, the majority of MCM7 is presented as a free form but its function is not well understood. It has been reported that MCM7 protein is localized in telomere, but its biological significance is not clear. Our preliminary data indicated that MCM7 can promote the telomerase activity while knockdownof MCM7 can cause the decrease of telomerase activity. Interestingly,we found that MCM7 can interact with telomerase catalytic subunit hTERT and also enhance the stability of hTERT protein. In order to investigate the mechanism of MCM7 in up-regulating the activity of hTERT and whether MCM7 can promote tumorigensis by influence telomerase activity, we plan to accomplish the following studies: (1) To identify the binding site or domain of MCM7 with hTERT, and examine whether MCM7 affects the association of hTERT and human telomerase RNA template (hTR); (2) It is known that phosphorylation of MCM7 by cyclin E/Cdk2 affects its chromatin localization. Therfore we will investigate whether the phosphorylation of MCM7 influences its function on regulating the subcellular localization of hTERT as well as its stability; (3) To establish the MCM7 and its mutant inducible cell lines and examine whether MCM7 promotes the cell proliferation,migration and tumorigenesis by up-regulating hTERT using mice model. (4) To study the clinical correlation of MCM7 and hTERT in hepatocarcinoma samples and reveal the relevance of MCM7 and hTERT in tumorigenesis as well as prognosis of HCC.