Bergstralh Daniel T, Sekelsky Jeff
Department of Biology, Program in Molecular Biology and Biotechnology, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Trends Genet. 2008 Feb;24(2):70-6. doi: 10.1016/j.tig.2007.11.003. Epub 2008 Jan 14.
The interstrand crosslink (ICL) presents a challenge to both the cell and the scientist. From a clinical standpoint, these lesions are particularly intriguing: ICL-inducing agents are powerful tools in cancer chemotherapy, and spontaneous ICLs have recently been linked with accelerated aging phenotypes. Nevertheless, the ICL repair process has proven difficult to elucidate. Here we discuss recent additions to the current model and argue that the endonuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1 (XPF-ERCC1) has been heretofore misplaced. During nucleotide excision repair, XPF-ERCC1 makes a single-strand nick adjacent to the lesion. XPF-ERCC1 has been thought to play an analogous role in ICL repair. However, recent data has implicated XPF-ERCC1 in homologous recombination. We suggest that this role, rather than its function in nucleotide excision repair, defines its importance to ICL repair.
链间交联（ICL）对细胞和科学家而言都是一项挑战。从临床角度来看，这些损伤尤其引人关注：诱导ICL的药物是癌症化疗中的有力工具，而且最近发现自发性ICL与加速衰老表型有关。然而，ICL修复过程已被证明难以阐明。在此我们讨论了当前模型的最新补充内容，并认为迄今为止，核酸内切酶着色性干皮病互补组F-切除修复交叉互补啮齿动物修复缺陷互补组1（XPF-ERCC1）的定位有误。在核苷酸切除修复过程中，XPF-ERCC1会在损伤相邻处产生一个单链切口。人们一直认为XPF-ERCC1在ICL修复中发挥类似作用。然而，最近的数据表明XPF-ERCC1参与同源重组。我们认为，这一作用而非其在核苷酸切除修复中的功能，决定了它对ICL修复的重要性。
