人类线粒体拓扑异构酶I。
Human mitochondrial topoisomerase I.
作者信息
Zhang H, Barceló J M, Lee B, Kohlhagen G, Zimonjic D B, Popescu N C, Pommier Y
机构信息
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10608-13. doi: 10.1073/pnas.191321998. Epub 2001 Aug 28.
Abstract
Tension generated in the circular mitochondrial genome during replication and transcription points to the need for mtDNA topoisomerase activity. Here we report a 601-aa polypeptide highly homologous to nuclear topoisomerase I. The N-terminal domain of this novel topoisomerase contains a mitochondrial localization sequence and lacks a nuclear localization signal. Therefore, we refer to this polypeptide as top1mt. The pattern of top1mt expression matches the requirement for high mitochondrial activity in specific tissues. top1mt is a type IB topoisomerase that requires divalent metal (Ca(2+) or Mg(2+)) and alkaline pH for optimum activity. The TOP1mt gene is highly homologous to the nuclear TOP1 gene and consists of 14 exons. It is localized on human chromosome 8q24.3.
摘要
线粒体环状基因组在复制和转录过程中产生的张力表明需要线粒体DNA拓扑异构酶活性。在此，我们报道了一种与核拓扑异构酶I高度同源的601个氨基酸的多肽。这种新型拓扑异构酶的N端结构域包含一个线粒体定位序列，且缺乏核定位信号。因此，我们将该多肽称为top1mt。top1mt的表达模式与特定组织中线粒体高活性的需求相匹配。top1mt是一种IB型拓扑异构酶，需要二价金属（Ca(2+)或Mg(2+)）和碱性pH以达到最佳活性。TOP1mt基因与核TOP1基因高度同源，由14个外显子组成。它定位于人类染色体8q24.3。
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本文引用的文献
1
Topoisomerase I inhibitors: selectivity and cellular resistance.拓扑异构酶I抑制剂：选择性与细胞耐药性。
Drug Resist Updat. 1999 Oct;2(5):307-318. doi: 10.1054/drup.1999.0102.
2
What regulates mitochondrial DNA copy number in animal cells?什么调节动物细胞中的线粒体DNA拷贝数？
Trends Genet. 2001 Apr;17(4):199-205. doi: 10.1016/s0168-9525(01)02238-7.
3
A novel nuclear localization signal in human DNA topoisomerase I.人类DNA拓扑异构酶I中的一种新型核定位信号。
J Biol Chem. 2000 Dec 29;275(52):41107-13. doi: 10.1074/jbc.M003135200.
4
Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]- pyrene diol epoxide adducts at the 6-amino group of adenine.嵌入的苯并[a]芘二醇环氧化物加合物在腺嘌呤的6-氨基处对拓扑异构酶I-DNA切割复合物进行位点特异性捕获。
Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10739-44. doi: 10.1073/pnas.190312697.
5
Induction of reversible complexes between eukaryotic DNA topoisomerase I and DNA-containing oxidative base damages. 7, 8-dihydro-8-oxoguanine and 5-hydroxycytosine.真核生物DNA拓扑异构酶I与含DNA的氧化碱基损伤之间可逆复合物的诱导。7,8-二氢-8-氧代鸟嘌呤和5-羟基胞嘧啶。
J Biol Chem. 1999 Mar 26;274(13):8516-23. doi: 10.1074/jbc.274.13.8516.
6
Mitochondrial disorders.线粒体疾病
Biochim Biophys Acta. 1999 Feb 9;1410(2):99-102. doi: 10.1016/s0005-2728(98)00160-1.
7
Mitochondrial diseases in man and mouse.人类和小鼠的线粒体疾病。
Science. 1999 Mar 5;283(5407):1482-8. doi: 10.1126/science.283.5407.1482.
8
Mitochondrial leader sequences: structural similarities and sequence differences.线粒体前导序列：结构相似性与序列差异
J Exp Zool. 1998;282(1-2):280-3.
9
Nuclear power and mitochondrial disease.核能与线粒体疾病
Nat Genet. 1998 Jul;19(3):214-5. doi: 10.1038/883.
10
Domains of human topoisomerase I and associated functions.人类拓扑异构酶I的结构域及相关功能。
Prog Nucleic Acid Res Mol Biol. 1998;60:111-32. doi: 10.1016/s0079-6603(08)60891-0.
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