Schirmacher P, Wang H, Stahnke G, Will H, Rogler C E
Marion Bessin Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, New York, NY 10461, USA.
J Hepatol. 1995;22(1 Suppl):21-33.
We have previously shown that eukaryotic topoisomerase I (topo I) can mediate hepadnaviral integration in vitro. To investigate further the possible in vivo significance of topo I in hepadnaviral integration and to detect additional important factors, we have generated an extensive compilation of hepadnaviral recombination sites from chronically infected liver tissues and hepatocellular carcinomas. These sequences were subjected to various established sequence and structural analyses. Our investigation provides evidence that topo I can mediate hepadnaviral integration and rearrangement in vivo. During integration, free ends can be exposed to other nuclear enzymes, resulting in the addition of 'filler DNA'. In other cases, junctional homologies between viral and cellular DNA may facilitate integration. Structural analysis suggests that torsional stress may act on the cellular target sites, possibly promoting the integration process. A mechanism is proposed by which hepadnavirus integration into the host chromosomes is primarily mediated by topo I.
我们之前已经表明，真核拓扑异构酶I（拓扑异构酶I）在体外可介导嗜肝DNA病毒整合。为了进一步研究拓扑异构酶I在嗜肝DNA病毒整合中可能的体内意义，并检测其他重要因素，我们从慢性感染的肝组织和肝细胞癌中收集了大量嗜肝DNA病毒重组位点。这些序列经过了各种既定的序列和结构分析。我们的研究提供了证据，证明拓扑异构酶I可在体内介导嗜肝DNA病毒整合和重排。在整合过程中，游离末端可能会暴露于其他核酶，从而导致“填充DNA”的添加。在其他情况下，病毒DNA与细胞DNA之间的连接同源性可能有助于整合。结构分析表明，扭转应力可能作用于细胞靶位点，可能促进整合过程。我们提出了一种机制，即嗜肝DNA病毒整合到宿主染色体主要由拓扑异构酶I介导。
