DNA-蛋白质共价交联是一种非常严重的DNA损伤，它会阻碍DNA正常的解旋及复制过程，导致细胞正常分裂受阻以至细胞死亡。Wss1是一种蛋白酶，它能够剪掉DNA-蛋白质交联中的蛋白组分，使生物体得以正常复制它们的遗传信息。目前对该蛋白的研究局限在细胞水平。对于其三维结构，及其与DNA，Cdc48，泛素等配体的相互作用机制还不清楚。本课题将以酿酒酵母的Wss1作为研究对象，利用X射线晶体学与小角散射相结合的方法解析其三维结构，并进一步研究Wss1与相关底物的相互作用，将其组装成均一稳定的复合物，尝试解析复合物结构。结合定点突变结果，找出Wss1与底物结合的相互作用位点，以及行使蛋白酶催化功能的活性位点，在分子水平上认识其参与修复DNA-蛋白质链间交联的过程和作用机理。研究成果将对基因组完整性和癌症发展的理解有重要意义，还将为新型抗癌药物的设计提供参考依据。

DNA–protein crosslinks (DPC) are highly toxic DNA lesions because they interfere with DNA transactions and lead to cell death. Wss1 is a kind of protease which is able to decompose the protein component of DPC and enables the living organism to replicate their genetic information normally. Nowadays, our knowledge about this protein is still limited in the cellular level. The three dimensional structure of Wss1, and its interactions with DNA, Cdc48, ubiquitin are still elusive. In this project, we aim to solve the structure of Wss1 from saccharomyces cerevisiae using X ray crystallography combined with small angle X-ray scattering (SAXS). Then, further efforts will be paid to find the catalytic sites of Wss1 using mutation experiments. The research will contribute to our knowledge about this protein in the molecular level, enable us to understand the mechanism of Wss1 in repairing DPC, and provide us a structural basis for designing anti-cancer drugs.