LRR212调控Nek1介导的DNA损伤修复及抗辐射研究

项目名称： LRR212调控Nek1介导的DNA损伤修复及抗辐射研究

项目编号： No.81472909

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王晓辉

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 70万元

中文摘要： 放射治疗是治疗癌症的有效方法之一，然而研究表明，电离辐射能引起各种细胞周期阻滞，使细胞不能进入有丝分裂，从而使肿瘤细胞可逃避射线杀伤并导致放射性抗拒，严重影响恶性肿瘤放疗效果，因此提高肿瘤辐射敏感性成为当前放疗研究的热点之一。Nek1是电离辐射诱导的激酶之一，Nek蛋白激酶家族是参与细胞有丝分裂调控的研究较少的激酶家族。Nek1的缺失增强细胞的的辐射敏感性。我们以Nek1为诱饵，利用免疫沉淀与质谱联合技术筛选到相互作用蛋白LRR212，并确定了相互作用及结合模式。我们发现LRR212敲除小鼠具有抗辐射能力，而且LRR212-/-MEF细胞对DNA损伤修复能力增强，凋亡减弱。因此，拟以LRR212在Nek1介导下影响DNA损伤修复为基础进行抗辐防辐射相关研究，为阐明抗辐射分子机理，加深Nek家族在细胞周期调控及相关疾病的分子机制理解提供坚实基础，并为相关疾病诊断和放射治疗打下基础。

中文关键词： 电离辐射；DNA损伤；Nek1；LRR212；细胞周期

英文摘要： Radiotherapy is one of the effective methods for the treatment of cancer, but the study showed ionizing radiation can cause cell cycle arrest, and make the cell not to enter mitosis. So that tumor cells can escape the ray killing, cause radioactive resistance, and serious impact on radiotherapy of malignant tumors. And then improving tumor radiosensitivity effect has become a hot topic in radiation research. Nek1 is one of the kinase induced by ionizing radiation, Nek family kinases are involved in mitotic regulation but we have little about them. Deletion of Nek1 enhanced radiosensitivity of cells. And then we made Nek1 as bait, using IP-MS to get the interacting protein, LRR212 is one of them. And we had determined the interaction and combination mode of them. We found that LRR212 knockout mice have anti radiation ability, and LRR212-/- enhanced DNA damage repair in MEF cell,and the apoptosis decreased. So, we study LRR212 regulate Nek1- mediated DNA damage repair, and then study ant- radiation and radiation protection.It is used to elucidate the molecular mechanism of anti- radiation,and used to understand the the molecular mechanism of cell cycle regulation and related diseases, and used for the diagnosis of related diseases and radiation therapy.

英文关键词： Ionizing radiation;DNA damage;Nek1;LRR212;cell cycle