Jones Mathew J K, Huang Tony T
Department of Biochemistry, New York University School of Medicine, 550 First Ave., MSB 399, New York, NY, 10016, USA.
Cell Mol Life Sci. 2012 Dec;69(23):3963-74. doi: 10.1007/s00018-012-1051-0. Epub 2012 Jun 29.
Interstand crosslinks (ICLs) are DNA lesions where the bases of opposing DNA strands are covalently linked, inhibiting critical cellular processes such as transcription and replication. Chemical agents that generate ICLs cause chromosomal abnormalities including breaks, deletions and rearrangements, making them highly genotoxic compounds. This toxicity has proven useful for chemotherapeutic treatment against a wide variety of cancer types. The majority of our understanding of ICL repair in humans has been uncovered through analysis of the rare genetic disorder Fanconi anemia, in which patients are extremely sensitive to crosslinking agents. Here, we discuss recent insights into ICL repair gained using new repair assays and highlight the role of the Fanconi anemia repair pathway during replication stress.
链间交联(ICLs)是一种DNA损伤,其中相对的DNA链的碱基通过共价键连接,从而抑制诸如转录和复制等关键细胞过程。产生ICLs的化学试剂会导致染色体异常,包括断裂、缺失和重排,使其成为具有高度遗传毒性的化合物。这种毒性已被证明对多种癌症类型的化疗治疗有用。我们对人类ICL修复的大部分理解是通过对罕见的遗传性疾病范可尼贫血的分析获得的,在这种疾病中,患者对交联剂极其敏感。在这里,我们讨论了使用新的修复检测方法对ICL修复的最新见解,并强调了范可尼贫血修复途径在复制应激中的作用。