DNA双链断裂是细胞受到电离辐射等因素破坏后生物学上最严重的损伤，其修复机制复杂且与肿瘤发病和治疗相关，研究DNA修复是探索生命的一个重要方面，也是医学和肿瘤学等领域的重要课题。DNA修复涉及到一系列复杂的物理过程，需要用物理方法解决。本项目中我们综合应用各种尖端单分子技术包括单粒子冷冻电镜、单分子磁镊和单分子荧光等，在纳米层次研究DNA断裂修复中的分子动态结构和酶功能关系、化学能与机械能转换机理、机械力对酶催化功能的调控以及小系统的热力学等关键物理问题，探索参与该过程的各分子机器及其复合物的动力学原理，归纳优化纳米机器结构设计的原则与热力学规律，为相关的医学和肿瘤学研究提供科学依据，为人工纳米机器的研究和制作提供仿生学借鉴。

Double-strand breaks (DSBs), in which both strands in the double helix are severed, are particularly hazardous to the cell because they can lead to genome rearrangements. Homologous recombination (HR) is one of the main pathways of DSB repair, in which nucleotide sequences are exchanged between two similar or identical molecules of DNA. Many protein machines are involved in HR, including exonucleases, recombinases, helicases and polymerases, and so on. In this project, by combining sub-nanometer-resolution fluorescence resonant energy transfer, individual particle cryo-electron microscopy and molecular dynamic simulation, we study a few key physical problems raised in HR, e.g., dynamical structures, chemo-mechanical transformations, force regulations and thermodynamics of small systems. The project aims in developing a research paradigm that we term snapshots sorting and animation to investigate the dynamics of HR and unveil the molecular mechanisms of protein machines involved in HR. We will be able to measure the action of a protein machine driven by the energy of hydrolysis of a single ATP molecule. Knowledges gained from our study will also be very helpful to design of man-made molecular machines.