Department of Carcinogenesis, Science Park-Research Division, University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA.
Environ Mol Mutagen. 2010 Jul;51(6):567-81. doi: 10.1002/em.20583.
DNA interstrand crosslinks (ICLs) are among the most deleterious cytotoxic lesions encountered by cells, mainly due to the covalent linkage these lesions create between the two strands of DNA which effectively blocks replication and transcription. Although ICL repair in mammalian cells is not fully understood, processing of these lesions is thought to begin by "unhooking" at the site of the damaged base accompanied by the generation of a double strand break and ultimately repair through translesion synthesis and homologous recombination. A key player in this repair process is the heterodimeric protein complex ERCC1-XPF. Although some models of ICL repair restrict ERCC1-XPF activity to the unhooking step, recent data suggest that this protein complex acts in additional downstream steps. Here, we review the evidence implicating ERCC1-XPF in multiple steps of ICL repair.
DNA 链间交联 (ICLs) 是细胞中遇到的最具细胞毒性的损伤之一，主要是因为这些损伤在 DNA 的两条链之间形成了共价键，有效地阻止了复制和转录。尽管哺乳动物细胞中的 ICL 修复尚未完全了解，但这些损伤的处理过程被认为是从损伤碱基处的“解连环”开始的，同时伴随着双链断裂的产生，并最终通过跨损伤合成和同源重组进行修复。在这个修复过程中，关键的参与者是异二聚体蛋白复合物 ERCC1-XPF。尽管一些 ICL 修复模型将 ERCC1-XPF 的活性限制在解连环步骤，但最近的数据表明，该蛋白复合物在其他下游步骤中发挥作用。在这里，我们回顾了 ERCC1-XPF 参与 ICL 修复多个步骤的证据。
