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在含有两个DNA复制起点的基因组中猿猴病毒40早期区域转录的异常调控

Unusual regulation of simian virus 40 early-region transcription in genomes containing two origins of DNA replication.

作者信息

Buchman A R, Berg P

出版信息

Mol Cell Biol. 1984 Sep;4(9):1915-28. doi: 10.1128/mcb.4.9.1915-1928.1984.

DOI:10.1128/mcb.4.9.1915-1928.1984
PMID:6092947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC369001/
Abstract

As part of our efforts to create multifunctional vectors for the transduction of animal cells, a set of simian virus 40 recombinants were constructed which contain an inverted duplication of the region including the origin of viral DNA replication (ori) and the early-region promoter. The unusual aspects of the structure of these recombinant genomes revealed several unexpected features of their function. In particular, transcription from the early-region promoters on these recombinants occurred primarily after the start of DNA replication, and, in that sense, these promoters behaved as if they were late-region promoters. This behavior results from the fact that these genomes contain multiple ori segments, and, therefore, they replicate earlier and faster than wild-type virus DNA, thereby causing a precocious shift in the initiation of early-region transcription from sites downstream of ori to sites located upstream of ori. The abnormal expression from multiple ori genomes is consistent with our present notions regarding the replication-dependent shift in early-region transcriptional start sites (Buchman et al., Mol. Cell. Biol. 4:1900-1914). Since our experiments demonstrate that RNAs initiated upstream of ori contribute to T-antigen formation late in infection, we suggest that the shift in early-region transcription starts modulates large T-antigen production in concert with viral DNA replication.

摘要

作为我们构建用于动物细胞转导的多功能载体的工作的一部分,构建了一组猴病毒40重组体,其包含包括病毒DNA复制起点(ori)和早期区域启动子的区域的反向重复序列。这些重组基因组结构的异常方面揭示了其功能的几个意外特征。特别是,这些重组体上早期区域启动子的转录主要发生在DNA复制开始之后,从这个意义上说,这些启动子的行为就好像它们是晚期区域启动子。这种行为是由于这些基因组包含多个ori片段,因此,它们比野生型病毒DNA更早、更快地复制,从而导致早期区域转录起始从ori下游位点早熟地转移到ori上游位点。多个ori基因组的异常表达与我们目前关于早期区域转录起始位点的复制依赖性转移的观点一致(Buchman等人,《分子与细胞生物学》4:1900 - 1914)。由于我们的实验表明在ori上游起始的RNA在感染后期有助于T抗原的形成,我们认为早期区域转录起始的转移与病毒DNA复制协同调节大T抗原的产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/94cce0254056/molcellb00151-0262-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/8815d8ac968a/molcellb00151-0255-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/61f400c35b1c/molcellb00151-0256-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/25a619d2a613/molcellb00151-0257-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/a9936420adc3/molcellb00151-0259-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/6fb1b8ee99dd/molcellb00151-0260-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/94cce0254056/molcellb00151-0262-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/8815d8ac968a/molcellb00151-0255-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/61f400c35b1c/molcellb00151-0256-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/25a619d2a613/molcellb00151-0257-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/a9936420adc3/molcellb00151-0259-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/6fb1b8ee99dd/molcellb00151-0260-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/369001/94cce0254056/molcellb00151-0262-a.jpg

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本文引用的文献

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Mutational dissection of the 21 bp repeat region of the SV40 early promoter reveals that it contains overlapping elements of the early-early and late-early promoters.对SV40早期启动子21bp重复区域的突变分析表明,它包含早期-早期启动子和晚期-早期启动子的重叠元件。
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Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter.
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