Lebedeva Natalia, Rechkunova Nadejda, Boiteux Serge, Lavrik Olga
Institute of Chemical Biology and Fundamental Medicine, Prospect Lavrentieva 8, 630090, Novosibirsk, Russia.
IUBMB Life. 2008 Feb;60(2):130-4. doi: 10.1002/iub.5.
In this report we show that human DNA Topoisomerase I (Top1) forms DNA-protein adducts with nicked and gapped DNA structures lacking a conventional Top1 cleavage site. The radioactively labeled crosslinking products were identified by SDS-gel electrophoresis. The chemical structure of the groups at 5' or 3' end of the nick does not have an effect on the formation of these covalent adducts. Therefore, all kinds of nicks, either directly induced by ionizing radiation or reactive oxygen species or indirectly induced in the course of base excision repair (BER) are targets for Top1 that competes with BER proteins and other nick-sensors. Top1-DNA covalent adducts formed in cells exposed to DNA damaging agents can promote genetic instability.
在本报告中，我们表明人类DNA拓扑异构酶I（Top1）与缺乏传统Top1切割位点的带切口和缺口的DNA结构形成DNA-蛋白质加合物。通过SDS-凝胶电泳鉴定放射性标记的交联产物。切口5'或3'端基团的化学结构对这些共价加合物的形成没有影响。因此，各种切口，无论是由电离辐射或活性氧直接诱导的，还是在碱基切除修复（BER）过程中间接诱导的，都是Top1的作用靶点，Top1会与BER蛋白和其他切口传感器竞争。暴露于DNA损伤剂的细胞中形成的Top1-DNA共价加合物可促进遗传不稳定性。
