Department of Biology, Tufts University, Medford, Massachusetts 02155, USA.
Environ Mol Mutagen. 2010 Jul;51(6):646-58. doi: 10.1002/em.20551.
DNA interstrand crosslinks (ICLs) are complex lesions that covalently link both strands of the DNA double helix and impede essential cellular processes such as DNA replication and transcription. Recent studies suggest that multiple repair pathways are involved in their removal. Elegant genetic analysis has demonstrated that at least three distinct sets of pathways cooperate in the repair and/or bypass of ICLs in budding yeast. Although the mechanisms of ICL repair in mammals appear similar to those in yeast, important differences have been documented. In addition, mammalian crosslink repair requires other repair factors, such as the Fanconi anemia proteins, whose functions are poorly understood. Because many of these proteins are conserved in simpler metazoans, nonmammalian models have become attractive systems for studying the function(s) of key crosslink repair factors. This review discusses the contributions that various model organisms have made to the field of ICL repair. Specifically, it highlights how studies performed with C. elegans, Drosophila, Xenopus, and the social amoeba Dictyostelium serve to complement those from bacteria, yeast, and mammals. Together, these investigations have revealed that although the underlying themes of ICL repair are largely conserved, the complement of DNA repair proteins utilized and the ways in which each of the proteins is used can vary substantially between different organisms.
DNA 链间交联（ICLs）是一种复杂的损伤，它将 DNA 双螺旋的两条链共价连接在一起，并阻碍 DNA 复制和转录等重要的细胞过程。最近的研究表明，多个修复途径参与了它们的去除。精心设计的遗传分析表明，在芽殖酵母中，至少有三组不同的途径合作修复和/或绕过 ICL。尽管哺乳动物中的 ICL 修复机制似乎与酵母中的相似，但已经记录了重要的差异。此外，哺乳动物的交联修复需要其他修复因子，如范可尼贫血蛋白，其功能尚未完全了解。由于这些蛋白质中的许多在更简单的后生动物中是保守的，因此非哺乳动物模型已成为研究关键交联修复因子功能的有吸引力的系统。本文综述了各种模式生物在 ICL 修复领域的贡献。具体来说，它强调了秀丽隐杆线虫、果蝇、非洲爪蟾和黏菌在 ICL 修复研究中的作用，这些研究补充了来自细菌、酵母和哺乳动物的研究。这些研究共同表明，尽管 ICL 修复的基本主题在很大程度上是保守的，但所利用的 DNA 修复蛋白的种类以及每种蛋白的使用方式在不同的生物体之间可能有很大的不同。
