Human mitochondrial topoisomerase I.
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.
Zhang
H
H
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Barceló
J M
JM
Lee
B
B
Kohlhagen
G
G
Zimonjic
D B
DB
Popescu
N C
NC
Pommier
Y
Y
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
D002413:Cations, Divalent; D004272:DNA, Mitochondrial; D010455:Peptides; D004264:DNA Topoisomerases, Type I; D008274:Magnesium; D002118:Calcium