人源CENP-A核小体/CENP-CLNHIKM复合物在动粒组装中的结构与功能研究
结题报告
批准号:
32000858
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
田甜
依托单位:
学科分类:
结构生物学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
田甜
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中文摘要
动粒是一个复杂的功能性蛋白质复合物,在有丝分裂过程中,为姐妹染色单体的准确分离提供必要条件。它的组装随细胞周期的进展可能会出现多个中间体,而研究这些中间体复合物的结构,对明确动粒组装机制而言不可或缺。. 本项目拟以人源CENP-A核小体/CENP-CLNHIKM复合物为研究对象,利用结构生物学、生物化学和细胞生物学方法,解析其高分辨率结构,阐明其在细胞有丝分裂过程中的功能,揭示其在动粒装配和在维持基因组稳定性过程中发挥的重要作用,为新型有丝分裂抑制剂的研发提供理论支持,也为治疗由非整倍体引起的疾病提供可能的靶点。
英文摘要
During mitosis, sister chromatids are precisely divided into two daughter cells to complete the transmission of genetic material, which is crucial for the healthy growth and development of organisms. The first condition for the accurate separation of sister chromatids is the correct attachment of spindle microtubules to centromeric-chromatin dependent on kinetochore. Kinetochore is a large functional protein complex, whose assembly on centromere is step by step as the development of cell cycle. In the process, many different intermediates may arise. However, the study of these intermediate complexes is essential to elucidate the mechanisms of kinetochore assembly. The specific recognition of CENP-N and CENP-C for CENP-A nucleosome and the recruitment of CENP-L/HIKM are crucial for kinetochore assembly.. In this project, we want to know the structural and functional mechanisms of CENP-A nucleosome/CENP-CLNHIKM complex in kinetochore assembly and how its regulation in cell mitosis. The result will reveal its important role in the assembly of kinetochore and the maintenance of genomic stability, and to provide a possible target for the treatment of related diseases.
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DOI:https://doi.org/10.1093/jmcb/mjad041
发表时间:2023
期刊:Journal of Molecular Cell Biology
影响因子:5.5
作者:Ran Liu;Zhen Dou;Tian Tian;Xinjiao Gao;Lili Chen;Xiao Yuan;Chunyue Wang;Jiahe Hao;Ping Gui;McKay Mullen;Felix Aikhionbare;Liwen Niu;Guoqiang Bi;Peng Zou;Xuan Zhang;Chuanhai Fu;Xuebiao Yao;Jianye Zang;Xing Liu
通讯作者:Xing Liu
国内基金
海外基金