Abstract：
Genomic interstrand crosslinks (ICLs) are formed by reactive species generated during normal cellular metabolism, produced by the microbiome, and employed in cancer chemotherapy. While there are multiple options for replication dependent and independent ICL repair, the crucial step for each is unhooking one DNA strand from the other. Much of our insight into mechanisms of unhooking comes from powerful model systems based on plasmids with defined ICLs introduced into cells or cell free extracts. Here we describe the properties of exogenous and endogenous ICL forming compounds and provide an historical perspective on early work on ICL repair. We discuss the modes of unhooking elucidated in the model systems, the concordance or lack thereof in drug resistant tumors, and the evolving view of DNA adducts, including ICLs, formed by metabolic aldehydes.
摘要：
基因组链间交联（ICL）是由正常细胞代谢过程中产生的反应物质形成的，由微生物组产生，并用于癌症化疗。虽然复制相关和独立的ICL修复有多种选择，每个人的关键步骤是将一条DNA链与另一条DNA链脱钩。我们对脱钩机制的许多见解来自强大的模型系统，该模型系统基于将定义的ICL引入细胞或无细胞提取物的质粒。在这里，我们描述了外源性和内源性ICL形成化合物的特性，并提供了ICL修复早期工作的历史观点。我们讨论了模型系统中阐明的脱钩模式，耐药肿瘤中的一致性或缺乏一致性，以及DNA加合物不断发展的观点，包括ICL,由代谢醛形成。
