title: Human mitochondrial topoisomerase I.
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.
authors.affiliation: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: J M
authors.initials: JM
authors.lastname: Barceló
authors.forename: B
authors.initials: B
authors.lastname: Lee
authors.forename: G
authors.initials: G
authors.lastname: Kohlhagen
authors.forename: D B
authors.initials: DB
authors.lastname: Zimonjic
authors.forename: N C
authors.initials: NC
authors.lastname: Popescu
authors.forename: Y
authors.initials: Y
authors.lastname: Pommier
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium; D002413:Cations, Divalent; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004264:DNA Topoisomerases, Type I / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005091:Exons; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008274:Magnesium; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D004272:DNA, Mitochondrial; D010455:Peptides; D004264:DNA Topoisomerases, Type I; D008274:Magnesium; D002118:Calcium