Bizelesin, a bifunctional cyclopropylpyrroloindole alkylating agent, inhibits simian virus 40 replication in trans by induction of an inhibitor.
Bizelesin, a bifunctional cyclopropylpyrroloindole alkylating agent, inhibits simian virus 40 replication in trans by induction of an inhibitor.
复制标题
Bizelesin 是一种双功能环丙基吡咯并吲哚烷化剂，通过抑制剂的诱导抑制猿病毒 40 反式复制。
DOI：
10.1021/bi990598r
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发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Beerman,TA
中科院分区：
文献类型：
--
作者：
McHugh,MM;Kuo,SR;Walsh-O'Beirne,MH;Liu,JS;Melendy,T;Beerman,TA
Bizelesin, a bifunctional DNA minor groove alkylating agent, inhibits both cellular and viral (SV40) DNA replication in whole cells. Bizelesin inhibition of SV40 DNA replication was analyzed in SV40-infected cells, using two-dimensional (2D) neutral agarose gel electrophoresis, and in a cell-free SV40 DNA replication assay. Within 1 h of bizelesin addition to infected cells, a similar rapid decrease in both the level of SV40 replication intermediates and replication activity was observed, indicating inhibition of initiation of SV40 DNA replication. However, prolonged bizelesin treatment (≥2 h) was associated with a reduced extent of elongation of SV40 replicons, as well as the appearance on 2D gels of intense spots, suggestive of replication pause sites. Inhibition of elongation and induction of replication pause sites may result from the formation of bizelesin covalent bonds on replicating SV40 molecules. The level of in vitro replication of SV40 DNA also was reduced when extracts from bizelesin-treated HeLa cells were used. This effect was not dependent upon the formation of bizelesin covalent bonds with the template DNA. Mixing experiments, using extracts from control and bizelesin-treated cells, indicated that reduced DNA replication competence was due to the presence of a trans-acting DNA replication inhibitor, rather than to decreased levels or inactivation of essential replication factor(s).
