DNA链间交联（ICL）是一种高毒性的DNA损伤，它通过抑制双链解旋来阻断细胞的转录翻译过程。一方面，若ICL不能及时清除将导致基因组的不稳定，造成癌症等重大病变；另一方面，DNA交联剂作为化疗药物广泛用于癌症治疗，癌细胞对ICL的修复是DNA交联药物产生抗药性的主要原因。因此，无论是对癌症发病机制的了解，还是对抗癌药物的研制，ICL修复机理研究都有十分重要的意义。本项目以可视化DNA交联剂为工具，利用DNA纤维荧光原位杂交技术研究DNA复制过程中的ICL修复过程；针对DNA复制过程中ICL如何“解锁”（unhooking），如何进行跨损伤DNA合成等问题进行探索；研究参与ICL修复蛋白的特异性，筛查可供干预的ICL修复靶标。本项目的完成将为了解癌症等疾病的发病机理提供新依据，为抗癌药物研制提供新策略。

Interstrand crosslinks (ICLs) are highly toxic DNA lesions that prevent transcription and replication by inhibiting double strands unwinding. Failure to resolve the ICL blocks will lead to genomic instability and cause serious diseases such as cancer. DNA crosslink agents are widely used as chemotherapeutic drugs. However, the repair of ICL by cancer cells results in drug resistance against DNA crosslink agents. Therefore, it has great significance for understanding cancer pathogenesis as well as developing anticancer drugs by ICL repair study. In this project, we will develop DNA fiber-fluorescence in situ hybridization to study ICL repair processes during DNA replication, especially for the mechanism of ICL unhooking and DNA translesion synthesis during ICL repair processes. The completion of this project will provide novel insights into the disease pathogenesis, and new strategies of cancer therapy.