CAMPTOTHECIN, A SPECIFIC INHIBITOR OF TYPE-I DNA TOPOISOMERASE, INDUCES DNA BREAKAGE AT REPLICATION FORKS
CAMPTOTHECIN, A SPECIFIC INHIBITOR OF TYPE-I DNA TOPOISOMERASE, INDUCES DNA BREAKAGE AT REPLICATION FORKS
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DOI：
10.1128/mcb.8.8.3026
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发表时间：
1988-08-01
影响因子：
5.3
通讯作者：
SOGO, JM
中科院分区：
文献类型：
--
作者：
AVEMANN, K;KNIPPERS, R;SOGO, JM
用生物化学和电子显微镜方法研究了从喜树碱处理的感染细胞中提取的复制型猿猴病毒40微型染色体的结构。我们发现，喜树碱经常诱导断裂复制叉接近复制生长点。复制分支在分叉的前导链和滞后链位点以大约相等的频率被破坏。由于喜树碱是已知的I型DNA拓扑异构酶的特异性抑制剂，我们认为，这种酶是非常接近的复制叉。这一结论得到了aphidicolin实验的支持，aphidicolin是一种阻断复制叉运动的药物，但不能阻止喜树碱诱导的复制叉断裂。药物替尼泊苷，一种II型DNA拓扑异构酶的抑制剂，对这些复制中间体的结构只有很小的影响。
The structure of replicating simian virus 40 minichromosomes, extracted from camptothecin-treated infected cells, was investigated by biochemical and electron microscopic methods. We found that camptothecin frequently induced breaks at replication forks close to the replicative growth points. Replication branches were disrupted at about equal frequencies at the leading and the lagging strand sites of the fork. Since camptothecin is known to be a specific inhibitor of type I DNA topoisomerase, we suggest that this enzyme is acting very near the replication forks. This conclusion was supported by experiments with aphidicolin, a drug that blocks replicative fork movement, but did not prevent the camptothecin-induced breakage of replication forks. The drug teniposide, an inhibitor of type II DNA topoisomerase, had only minor effects on the structure of these replicative intermediates.