Department of Biochemistry and Cancer Biology, University of Toledo - Health Science Campus, Toledo, OH 43614, USA.
Mutat Res. 2013 Mar-Apr;743-744:44-52. doi: 10.1016/j.mrfmmm.2012.11.007. Epub 2012 Dec 3.
Many bifunctional alkylating agents and anticancer drugs exert their cytotoxicity by producing cross links between the two complementary strands of DNA, termed interstrand crosslinks (ICLs). This blocks the strand separating processes during DNA replication and transcription, which can lead to cell cycle arrest and apoptosis. Cells use multiple DNA repair systems to eliminate the ICLs. Concerted action of repair proteins involved in Nucleotide Excision Repair and Homologous Recombination pathways are suggested to play a key role in the ICL repair. However, recent studies indicate a possible role for Base Excision Repair (BER) in mediating the cytotoxicity of ICL inducing agents in mammalian cells. Elucidating the mechanism of BER mediated modulation of ICL repair would help in understanding the recognition and removal of ICLs and aid in the development of potential therapeutic agents. In this review, the influence of BER proteins on ICL DNA repair and the possible mechanisms of action are discussed.
许多双功能烷化剂和抗癌药物通过在 DNA 的两条互补链之间产生交联来发挥其细胞毒性，这种交联被称为链间交联（ICLs）。这会阻止 DNA 复制和转录过程中的链分离，从而导致细胞周期停滞和细胞凋亡。细胞使用多种 DNA 修复系统来消除 ICLs。涉及核苷酸切除修复和同源重组途径的修复蛋白的协同作用被认为在 ICL 修复中发挥关键作用。然而，最近的研究表明，碱基切除修复（BER）可能在调节哺乳动物细胞中 ICL 诱导剂的细胞毒性方面发挥作用。阐明 BER 介导的 ICL 修复调节的机制将有助于理解 ICL 的识别和去除，并有助于开发潜在的治疗剂。在这篇综述中，讨论了 BER 蛋白对 ICL DNA 修复的影响及其可能的作用机制。
