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首页> 外文期刊>Biochemistry >DNA-damaging enediyne C-1027 inhibits initiation of intracellular SV40 DNA replication in trans.
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DNA-damaging enediyne C-1027 inhibits initiation of intracellular SV40 DNA replication in trans.

机译：破坏DNA的烯二炔C-1027抑制细胞内SV40 DNA反式复制的启动。

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摘要

This study used 2-D agarose gel techniques to examine the effects of the DNA-strand scission enediyne C-1027 on DNA replication in SV40-infected BSC-1 cells. Replication of SV40 DNA was inhibited by C-1027 to a greater extent than was BSC-1 genomic DNA replication in infected cells. Low nanomolar concentrations (0.2-10 nM) of C-1027 affected a rapid, progressive decrease in SV40 replication activity and replication intermediates (RIs) within 15 min after drug addition. A concurrent decrease in the signal of both the SV40 bubble arc and replication activity with increasing concentrations of C-1027 suggested that C-1027 inhibited initiation of new RIs. Additionally, the reduction in bubble arc signal observed with C-1027 was prevented when elongation of nascent chains was blocked by aphidicolin. Thus, the C-1027-induced disappearance of RIs probably is related to the maturation of preformed replication molecules in the absence of initiation of new RIs. Strand damage to SV40 DNA was barely detectable at concentrations where inhibition of replication activity was nearly complete, indicating that C-1027 replication inhibition occurs in trans.
机译：这项研究使用2-D琼脂糖凝胶技术检查了DNA断裂的烯二炔C-1027对SV40感染的BSC-1细胞中DNA复制的影响。 SV40 DNA的复制被C-1027抑制的程度大于BSC-1基因组DNA在感染细胞中的复制。加入药物后15分钟内，低纳摩尔浓度（0.2-10 nM）的C-1027影响了SV40复制活性和复制中间体（RIs）的快速，逐步下降。随着C-1027浓度的增加，SV40气泡电弧和复制活性的信号同时降低，表明C-1027抑制了新RI的启动。此外，当蚜虫二肽阻止新生链的延伸时，可防止使用C-1027观察到的气泡电弧信号降低。因此，C-1027诱导的RI消失可能与在没有新RI引发的情况下预先形成的复制分子的成熟有关。在复制活性的抑制作用几乎完全消失的浓度下，几乎无法检测到对SV40 DNA的链损伤，表明C-1027复制抑制发生在反式中。

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