Studies on mitochondrial type I topoisomerase and on its function

Fairfield, Frederic R.; Bauer, William R.; Simpson, Melvin V.

doi:10.1016/0167-4781(85)90028-4

Cited by 28 publications

(13 citation statements)

References 32 publications

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“…The optimum activity of top1mt at alkaline pH, whereas the pH optimum for nuclear top1 is at neutral or acidic pH, fits the known pH values for the mitochondrion and the nucleus, respectively (39). Activity of purified mitochondrial top1 at alkaline pH has also been reported (14,15,18,19,23,25). Thus, it is likely that the top1mt cloned in this study corresponds to the previously isolated enzyme activities.…”

Section: Discussionmentioning

confidence: 82%

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Human mitochondrial topoisomerase I

Zhang

Barceló

Lee

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

194

193

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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. DNA topoisomerases are enzymes that modify DNA topology by introducing reversible breaks in the DNA phosphodiester backbone. Topoisomerases are ubiquitous and essential for DNA strand separation, chromatin compaction, and DNA decatenation during replication and recombination. The first topoisomerase was identified in Escherichia coli in 1971 (1), and the existence of additional topoisomerases led to their classification into two types based on their enzymatic intermediates. The catalytic intermediate of type I topoisomerases is a DNA single-strand break. Type I enzymes have been subdivided further into two groups: type IA and type IB. Type IA enzymes break the DNA by forming a covalent bond to the 5Ј end of the broken DNA, whereas type IB topoisomerases bind covalently to the 3Ј end of the break (2, 3). The catalytic intermediate of type II topoisomerases is a DNA double-strand break with one enzyme molecule bound to each of the 5Ј ends of the doublestrand break (2-4). Until the present report, to our knowledge, two topoisomerase II genes (TOP2␣ and TOP2␤), two topoisomerase III genes (TOP3␣ and TOP3␤), and only one topoisomerase

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Section: Discussionmentioning

confidence: 82%

“…The presence of mitochondrial top1 activity has been reported in mammalian cells (human leukemia cells, human platelets, calf thymus, bovine and rat liver, and mouse leukemia L cells; refs. [11][12][13][14][15][16][17][18][19], Xenopus oocytes (20), plants (21,22), neurospora crassa (23), and yeast Saccharomyces cerevisiae (YSC; refs. [24][25][26].…”

mentioning

confidence: 99%

Human mitochondrial topoisomerase I

Zhang

Barceló

Lee

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

194

193

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“…Various enzymes probably involved in this process have been identified (12,13,14,15,16,17,18). The mitochondrial DNA polymerase activity has been definitely attributed to DNA polymerase.…”

Section: Introductionmentioning

confidence: 99%

“…More recently, a DNA primase activity has been characterized in a fraction active in priming mitochondrial DNA synthesis at the OL (18,21). Lastly, some reports have documented the presence of a DNA topoisomerase I acitivity inside mitochondria (15,22). Among the proteins without any known enzymatic activity that can interact with mitochondrial DNA, proteins binding preferentially to the region of the origin of replication have been found (23,24).…”

Section: Introductionmentioning

confidence: 99%

DNA curvature in front of the human mitochondrial L-strand replication origin with specific protein binding

et al. 1989

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DNA bending has been suggested to play a role in the regulation of gene expression, initiation of DNA-replication, site specific recombination, and DNA packaging. In the human mitochondrial DNA we have found a DNA curvature structure within the 3'-region of ther URF2 sequence in front of the L-strand origin of replication. This structure interacts specifically with a protein factor isolated from mitochondria. Based on the localization of this DNA curvature structure and the known function of such structures the data suggest a model in which this DNA signal sequence and its specific protein binding is involved in the regulatory initiation event of L-strand replication. INTRODUCTIONRecent studies have provided increasing evidence that certain DNA regions show a curved structure and that this curvature correlates with the periodical distribution of some dinucleotides along these molecules. The term 'curved DNA' refers to molecules which are curvilinear rather than straight without application of any external forces, as opposed to 'bent DNA', forcibly deformed (1). The locally curved DNA possibly is a sequencedependent feature recognized by some proteins (2,3,4). Proteins that induce or stabilize bends in specific DNA sequences are involved in a variety of cellular processes including site-specific recombination (5), DNA replication (6,7,8), chromatin organization (1) and gene regulation (9). Since the electrophoretic mobility of DNA fragments gels is dependent on their average shape, a curved DNA molecule migrates at a different rate than a linear fragment with the same number of base pairs; bent protein-DNA complexes behave in a analogous manner. A number of duplex DNA molecules obtained as restriction fragments from both, prokaryotic and eukaryotic sources, display distinctly anomalous electrophoretic behavior. The behavior is characterized by reduced electrophoretic mobilities of the restriction fragments on polyacrylamide gels. It is thought that the fragment's curvature hinders its mobility through a gel. This striking similarity between all the known curved fragments of DNA is constituted by the periodic presence of short adenine residues runs. In a few cases, the curved site has been shown to be within these periodic runs of A's (8,9,10).Our present data suggest such a natural DNA curvature in human mitochondrial genome.

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“…Mammalian nuclear topoisomerases do not seem to be inhibited in vitro by quinolones at relevant concentrations. Mammalian mitochondria resemble bacteria in numerous ways and are thought to possess their own DNA topoisomerases, independent from nucleus-originated ones (6,11,12). The function of these putative mammalian enzymes has been tested as a potential target of DNA gyrase inhibitors, with no convincing result (7,37 (23,33) and the yeast Saccharomyces cerevisiae (29).…”

mentioning

confidence: 99%

Cytofluorometric analysis of chondrotoxicity of fluoroquinolone antimicrobial agents

Hayem

Petit

Levacher

et al. 1994

Antimicrob Agents Chemother

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To better understand quinolone-related arthropathy, we conceived an experimental ex vivo model using cell cultures of articular chondrocytes issued from pretreated New Zealand White rabbits (NZW). Juvenile (4-to 5-week-old) NZW were orally dosed with ofloxacin or pefloxacin (300 mg/kg of body weight for 1 day) or with pefloxacin (300 mg/kg for 7 days). Adult (5-month-old) NZW were treated with pefloxacin (300 mg/kg for 1 day). Chondrocytes were enzymatically recovered from cartilage and were analyzed by cytofluorometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR), reflecting cellular respiratory-burst activity, and rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), specific for the mitochondrial activity and mass, respectively. A significant increase in the respiratory burst was detected by DCFH-DA and DHR in all treated groups of young animals, compared with untreated control groups. No significant increase of respiratory burst was noted in older treated rabbits. The 7-day treatment resulted in a decrease in mitochondrial uptake of Rh123 and an increase in NAO uptake. Fluoroquinolone arthrotoxicity seems to involve in its early phase the respiratory burst of immature articular chondrocytes.

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Studies on mitochondrial type I topoisomerase and on its function

Cited by 28 publications

References 32 publications

Human mitochondrial topoisomerase I

Human mitochondrial topoisomerase I

DNA curvature in front of the human mitochondrial L-strand replication origin with specific protein binding

Cytofluorometric analysis of chondrotoxicity of fluoroquinolone antimicrobial agents

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