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线粒体拓扑异构酶II活性对于动质体DNA微环分离至关重要。

Mitochondrial topoisomerase II activity is essential for kinetoplast DNA minicircle segregation.

作者信息

Shapiro T A

机构信息

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185.

出版信息

Mol Cell Biol. 1994 Jun;14(6):3660-7. doi: 10.1128/mcb.14.6.3660-3667.1994.

DOI:10.1128/mcb.14.6.3660-3667.1994
PMID:8196610
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC358733/
Abstract

Etoposide, a nonintercalating antitumor drug, is a potent inhibitor of topoisomerase II activity. When Trypanosoma equiperdum is treated with etoposide, cleavable complexes are stabilized between topoisomerase II and kinetoplast DNA minicircles, a component of trypanosome mitochondrial DNA (T. A. Shapiro, V. A. Klein, and P. T. Englund, J. Biol. Chem. 264:4173-4178, 1989). Etoposide also promotes the time-dependent accumulation of small minicircle catenanes. These catenanes are radiolabeled in vivo with [3H]thymidine. Dimers are most abundant, but novel structures containing up to five noncovalently closed minicircles are detectable. Analysis by two-dimensional gel electrophoresis and electron microscopy indicates that dimers joined by up to six interlocks are late replication intermediates that accumulate when topoisomerase II activity is blocked. The requirement for topoisomerase II is particularly interesting because minicircles do not share the features postulated to make this enzyme essential in other systems: for minicircles, the replication fork is unidirectional, access to the DNA is not blocked by nucleosomes, and daughter circles are extensively nicked and (or) gapped.

摘要

依托泊苷是一种非嵌入性抗肿瘤药物，是拓扑异构酶II活性的强效抑制剂。当用依托泊苷处理马媾疫锥虫时，拓扑异构酶II与动质体DNA小环（锥虫线粒体DNA的一个组成部分）之间的可切割复合物会稳定下来（T. A. 夏皮罗、V. A. 克莱因和P. T. 英格伦德，《生物化学杂志》264:4173 - 4178，1989年）。依托泊苷还会促进小环连环体随时间的积累。这些连环体在体内用[3H]胸腺嘧啶核苷进行放射性标记。二聚体最为丰富，但含有多达五个非共价闭合小环的新结构也可检测到。二维凝胶电泳和电子显微镜分析表明，由多达六个互锁连接的二聚体是拓扑异构酶II活性受阻时积累的晚期复制中间体。对拓扑异构酶II的需求特别有趣，因为小环并不具备在其他系统中假定使该酶必不可少的特征：对于小环来说，复制叉是单向的，DNA的进入不会被核小体阻断，并且子代环有大量切口和（或）缺口。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/0649529ab235/molcellb00006-0147-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/fa7124a67772/molcellb00006-0144-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/54378412c9fe/molcellb00006-0145-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/c9261478cca0/molcellb00006-0145-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/078650038fd9/molcellb00006-0146-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/0649529ab235/molcellb00006-0147-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/fa7124a67772/molcellb00006-0144-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/54378412c9fe/molcellb00006-0145-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/c9261478cca0/molcellb00006-0145-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/078650038fd9/molcellb00006-0146-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c62/358733/0649529ab235/molcellb00006-0147-a.jpg

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