染色质重塑因子通过改变核小体组蛋白的位置、组分来影响染色质的结构进而调节DNA的复制、转录、重组以及损伤修复。染色质重塑因子的核心成分是一类属于Snf2家族的依赖ATP水解提供能量的解旋酶。依据ATP酶相关序列的同源性，Snf2家族蛋白可分为24个亚家族，酵母Fun30/Fft3属于Etl1亚家族。Fun30/Fft3在DNA双链断裂修复、异染色质结构的维持及中心粒结构的维持方面发挥着重要的作用。然而Fun30/Fft3是如何识别染色质核小体而发挥作用的结构基础仍然不是很清楚。本项目申请拟重点以X-射线晶体学和冷冻电镜单颗粒技术作为主要研究手段，配合生物化学、分子生物学与细胞生物学等方法，系统地开展Fun30/Fft3与核小体复合物的结构与功能研究。

By sliding or moving the histone octamer to a new position, or displacing the octamer component，chromatin remodelers participate in the regulation of DNA replication, transcription，recombination and DNA-damage response. The core element of chromatin remodelers are helicase-like ATP-hydrolyzing machines that consist of the Snf2 helicase family. Snf2 family can be identified into 24 distinct subfamilies accroding to the multiple sequence alignment of the ATPase-related regions. Yeast Fun30/Fft3 belong to the Etl1 subfamily. Fun30/Fft3 plays important role in DNA double-strand breaks repair, maintain heterochromatin structure and centromeric stability. However, it is poorly understood how Fun30/Fft3 plays role in nucleosome targeting mechanism, regulation, and specialization for particular biological processes. This application will combine X-ray crystallography，Single-particle cryo-electron microscopy with biochemical methods and cell biology to investigate structure, assembly and working mechanism of the Fun30/Fft3-Nucleosome complex.