DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.
DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.
Enzymes that regulate the topology of DNA by actions such as breaking, relaxing, passing, and rejoining strands of DNA in cells. These enzymes are important components of the DNA replication system. They are classified by their substrate specificities. DNA TOPOISOMERASE I enzymes act on a single strand of DNA. DNA TOPOISOMERASE II enzymes act on double strands of DNA.
Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.
Compounds that inhibit the activity of DNA TOPOISOMERASES.
Compounds that inhibit the activity of DNA TOPOISOMERASE I.
Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.
A cardiotonic glycoside isolated from Scilla maritima var. alba (Squill).
An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.
CIRCULAR DNA that is interlaced together as links in a chain. It is used as an assay for the activity of DNA TOPOISOMERASES. Catenated DNA is attached loop to loop in contrast to CONCATENATED DNA which is attached end to end.
Complex compounds where two cyclic molecules are interlaced together as links in a chain. They have potential use in NANOTECHNOLOGY.
A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.
A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Topoisomerase IV binds to DNA as a heterotetramer consisting 2 parC and 2 parE subunits. Topoisomerase IV is a decatenating enzyme that resolves interlinked daughter chromosomes following DNA replication.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.
An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189)
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.
Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.
Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992)
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The process by which a DNA molecule is duplicated.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
A reaction that severs one of the covalent sugar-phosphate linkages between NUCLEOTIDES that compose the sugar phosphate backbone of DNA. It is catalyzed enzymatically, chemically or by radiation. Cleavage may be exonucleolytic - removing the end nucleotide, or endonucleolytic - splitting the strand in two.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Pyrido-CARBAZOLES originally discovered in the bark of OCHROSIA ELLIPTICA. They inhibit DNA and RNA synthesis and have immunosuppressive properties.
A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.
Acridines which are substituted in any position by one or more amino groups or substituted amino groups.
The rate dynamics in chemical or physical systems.
A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.
A genus of parasitic protozoans found in the digestive tract of invertebrates, especially insects. Organisms of this genus have an amastigote and choanomastigote stage in their life cycle.
A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.
DNA of kinetoplasts which are specialized MITOCHONDRIA of trypanosomes and related parasitic protozoa within the order KINETOPLASTIDA. Kinetoplast DNA consists of a complex network of numerous catenated rings of two classes; the first being a large number of small DNA duplex rings, called minicircles, approximately 2000 base pairs in length, and the second being several dozen much larger rings, called maxicircles, approximately 37 kb in length.
COUMARINS with an amino group, exemplified by NOVOBIOCIN.
Agents that are capable of inserting themselves between the successive bases in DNA, thus kinking, uncoiling or otherwise deforming it and therefore preventing its proper functioning. They are used in the study of DNA.
Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Naphthyridines are a class of heterocyclic organic compounds containing a naphthyridine nucleus, which is a polycyclic aromatic hydrocarbon made up of two benzene rings fused to a pyridine ring, and they have been studied for their potential pharmacological properties, including as antimicrobial, antiviral, and anticancer agents.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
A family of fused-ring hydrocarbons isolated from coal tar that act as intermediates in various chemical reactions and are used in the production of coumarone-indene resins.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A broad category of enzymes that are involved in the process of GENETIC RECOMBINATION.
QUINOLONES containing a 4-oxo (a carbonyl in the para position to the nitrogen). They inhibit the A subunit of DNA GYRASE and are used as antimicrobials. Second generation 4-quinolones are also substituted with a 1-piperazinyl group at the 7-position and a fluorine at the 6-position.
A genus of aerobic, chemolithotrophic, coccoid ARCHAEA whose organisms are thermoacidophilic. Its cells are highly irregular in shape, often lobed, but occasionally spherical. It has worldwide distribution with organisms isolated from hot acidic soils and water. Sulfur is used as an energy source.
Electrophoresis in which agar or agarose gel is used as the diffusion medium.
Triterpenes are a class of naturally occurring compounds consisting of six isoprene units arranged to form a 30-carbon skeleton, often found in plants and some animals, with various bioactivities including anti-inflammatory, antiviral, and cytotoxic properties.

Phylogenetic structures of the genus Acinetobacter based on gyrB sequences: comparison with the grouping by DNA-DNA hybridization. (1/2086)

The phylogenetic relationships of 49 Acinetobacter strains, 46 of which have previously been classified into 18 genomic species by DNA-DNA hybridization studies, were investigated using the nucleotide sequence of gyrB, the structural gene for the DNA gyrase B subunit. The phylogenetic tree showed linkages between genomic species 1 (Acinetobacter calcoaceticus), 2 (Acinetobacter baumannii), 3 and TU13; genomic species 6, BJ15, BJ16 and BJ17; genomic species 5, BJ13 (synonym of TU14) and BJ14; genomic species 7 (Acinetobacter johnsonii), 10 and 11; and genomic species 8 and 9. The phylogenetic grouping of Acinetobacter strains based on gyrB genes was almost congruent with that based on DNA-DNA hybridization studies. Consequently, gyrB sequence comparison can be used to resolve the taxonomic positions of bacterial strains at the level of genomic species. However, minor discrepancies existed in the grouping of strains of genomic species 8, 9 and BJ17. The phylogenetic tree for these strains was reconstructed from the sequence of rpoD, the structural gene for the RNA polymerase sigma 70 factor. The latter tree was 100% congruent with the grouping based on DNA-DNA hybridization. The reliability of DNA-DNA hybridization may be superior to that of sequence comparison of a single protein-encoding gene in resolving closely related organisms since the former method measures the homologies between the nucleotide sequences of total genomic DNAs. Three strains that have not been characterized previously by DNA-DNA hybridization seem to belong to two new genomic species, one including strain ATCC 33308 and the other including strains ATCC 31012 and MBIC 1332.  (+info)

Cloning, expression, and enzymatic characterization of Pseudomonas aeruginosa topoisomerase IV. (2/2086)

The topoisomerase IV subunit A gene, parC homolog, has been cloned and sequenced from Pseudomonas aeruginosa PAO1, with cDNA encoding the N-terminal region of Escherichia coli parC used as a probe. The homolog and its upstream gene were presumed to be parC and parE through sequence homology with the parC and parE genes of other organisms. The deduced amino acid sequence of ParC and ParE showed 33 and 32% identity with that of the P. aeruginosa DNA gyrase subunits, GyrA and GyrB, respectively, and 69 and 75% identity with that of E. coli ParC and ParE, respectively. The putative ParC and ParE proteins were overexpressed and separately purified by use of a fusion system with a maltose-binding protein, and their enzymatic properties were examined. The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. So, the cloned genes were identified as P. aeruginosa topoisomerase IV genes. The inhibitory effects of quinolones on the activities of topoisomerase IV and DNA gyrase were compared. The 50% inhibitory concentrations of quinolones for the decatenation activity of topoisomerase IV were from five to eight times higher than those for the supercoiling activities of P. aeruginosa DNA gyrase. These results confirmed that topoisomerase IV is less sensitive to fluoroquinolones than is DNA gyrase and may be a secondary target of new quinolones in wild-type P. aeruginosa.  (+info)

Fluoroquinolone action against clinical isolates of Mycobacterium tuberculosis: effects of a C-8 methoxyl group on survival in liquid media and in human macrophages. (3/2086)

When the lethal action of a C-8 methoxyl fluoroquinolone against clinical isolates of Mycobacterium tuberculosis in liquid medium was measured, the compound was found to be three to four times more effective (as determined by measuring the 90% lethal dose) than a C-8-H control fluoroquinolone or ciprofloxacin against cells having a wild-type gyrA (gyrase) gene. Against ciprofloxacin-resistant strains, the C-8 methoxyl group enhanced lethality when alanine was replaced by valine at position 90 of the GyrA protein or when aspartic acid 94 was replaced by glycine, histidine, or tyrosine. During infection of a human macrophage model by wild-type Mycobacterium bovis BCG, the C-8 methoxyl group lowered survival 20- to 100-fold compared with the same concentration of a C-8-H fluoroquinolone. The C-8 methoxyl fluoroquinolone was also more effective than ciprofloxacin against a gyrA Asn94 mutant of M. bovis BCG. In an M. tuberculosis-macrophage system the C-8 methoxyl group improved fluoroquinolone action against both quinolone-susceptible and quinolone-resistant clinical isolates. Thus, a C-8 methoxyl group enhances the bactericidal activity of quinolones with N1-cyclopropyl substitutions; these data encourage further refinement of fluoroquinolones as antituberculosis agents.  (+info)

Effect of cellular ATP depletion on topoisomerase II poisons. Abrogation Of cleavable-complex formation by etoposide but not by amsacrine. (4/2086)

Topoisomerase (topo) II poisons have been categorized into ATP-independent and -dependent drugs based on in vitro studies. We investigated drug-induced topoII-DNA complexes in intact cells almost completely depleted of ATP. Virtually no DNA single-strand breaks (SSBs), as measured by alkaline elution, were detected in energy-depleted cells treated with the topoII poisons etoposide, teniposide, daunorubicin, doxorubicin, mitoxantrone, or clerocidin. This inhibition was reversible; subsequent incubation with glucose restored the level of DNA SSBs. The effect of ATP depletion was specific for topoII, because topoI-mediated cleavable complexes induced by camptothecin were unaffected by ATP depletion. Furthermore, etoposide-induced DNA-protein complexes and DNA double-strand breaks, as measured by filter elution techniques, and topoIIalpha and -beta trapping, as measured by a band depletion assay, were completely inhibited by energy depletion. Differences in drug transport could not explain the effect of ATP depletion. The topoII poison amsacrine (m-AMSA) was unique with respect to ATP dependence. In ATP-depleted cells, m-AMSA-induced DNA SSBs, DNA double-strand breaks, DNA-protein complexes, topoIIalpha and -beta trapping were only modestly reduced. The accumulation of m-AMSA was reduced in ATP-depleted cells, which indicates that drug transport could contribute to the modest decrease in m-AMSA-induced cleavable complexes. In conclusion, drug-induced topoII-DNA complexes were completely antagonized in ATP-depleted cells, except in the case of m-AMSA. One possible interpretation is that m-AMSA mainly produces prestrand passage DNA lesions, whereas the other topoII poisons tested exclusively stabilize poststrand passage DNA lesions in intact cells.  (+info)

Mutation of a conserved serine residue in a quinolone-resistant type II topoisomerase alters the enzyme-DNA and drug interactions. (5/2086)

A Ser740 --> Trp mutation in yeast topoisomerase II (top2) and of the equivalent Ser83 in gyrase results in resistance to quinolones and confers hypersensitivity to etoposide (VP-16). We characterized the cleavage complexes induced by the top2(S740W) in the human c-myc gene. In addition to resistance to the fluoroquinolone CP-115,953, top2(S740W) induced novel DNA cleavage sites in the presence of VP-16, azatoxin, amsacrine, and mitoxantrone. Analysis of the VP-16 sites indicated that the changes in the cleavage pattern were reflected by alterations in base preference. C at position -2 and G at position +6 were observed for the top2(S740W) in addition to the previously reported C-1 and G+5 for the wild-type top2. The VP-16-induced top2(S740W) cleavage complexes were also more stable. The most stable sites had strong preference for C-1, whereas the most reversible sites showed no base preference at positions -1 or -2. Different patterns of DNA cleavage were also observed in the absence of drug and in the presence of calcium. These results indicate that the Ser740 --> Trp mutation alters the DNA recognition of top2, enhances its DNA binding, and markedly affects its interactions with inhibitors. Thus, residue 740 of top2 appears critical for both DNA and drug interactions.  (+info)

DNA topoisomerase IIalpha and -beta expression in human ovarian cancer. (6/2086)

To study DNA topoisomerase IIalpha (Topo-IIalpha) and -beta expression and regulation in human ovarian cancer, 15 ovarian tumour samples were investigated. To compare different levels of expression, the samples were screened for topo IIalpha and -beta mRNA with Northern blotting and a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay for Topo-IIalpha mRNA. Additionally, protein levels were determined with Western blotting and topoisomerase II activity levels with the decatenation assay. The results obtained were compared with each other and with the tumour volume index of the samples. In tumours with a tumour volume index > or = 50%, the mRNA levels (as determined by Northern blotting) and protein levels for each isozyme were in accordance. Additionally, correlations were found between Topo-IIalpha RT-PCR data and Topo-IIalpha Northern blot results, and between Topo-IIalpha RT-PCR data and Topo-IIalpha protein levels. Interestingly, Topo-IIbeta protein levels correlated better with Topo-II activity than Topo-IIalpha protein levels. In eight ovarian cystadenoma samples, no Topo-IIalpha protein could be found. In only three out of eight of these cystadenomas, Topo-IIbeta protein could be detected. These findings suggest that Topo-IIalpha and Topo-IIbeta protein levels are up-regulated in ovarian cancer and may indicate that Topo-IIbeta is an interesting target for chemotherapy in ovarian tumours.  (+info)

Analysis of DNA cleavage by reverse gyrase from Sulfolobus shibatae B12. (7/2086)

Reverse gyrase is a type I-5' topoisomerase, which catalyzes a positive DNA supercoiling reaction in vitro. To ascertain how this reaction takes places, we looked at the DNA sequences recognized by reverse gyrase. We used linear DNA fragments of its preferred substrate, the viral SSV1 DNA, which has been shown to be positively supercoiled in vivo. The Sulfolobus shibatae B12 strain, an SSV1 virus host, was chosen for production of reverse gyrase. This naturally occurring system (SSV1 DNA-S. shibatae reverse gyrase) allowed us to determine which SSV1 DNA sequences are bound and cleaved by the enzyme with particularly high selectivity. We show that the presence of ATP decreases the number of cleaved complexes obtained whereas the non-hydrolyzable ATP analog adenosine 5'-[beta, gamma-imido]triphosphate increases it without changing the sequence specificity.  (+info)

Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for isoform evolution through gene duplication. (8/2086)

Human DNA topoisomerase II is essential for chromosome segregation and is the target for several clinically important anticancer agents. It is expressed as genetically distinct alpha and beta isoforms encoded by the TOP2alpha and TOP2beta genes that map to chromosomes 17q21-22 and 3p24, respectively. The genes display different patterns of cell cycle- and tissue-specific expression, with the alpha isoform markedly upregulated in proliferating cells. In addition to the fundamental role of TOP2alpha and TOP2beta genes in cell growth and development, altered expression and rearrangement of both genes are implicated in anticancer drug resistance. Here, we report the complete structure of the human topoisomerase IIalpha gene, which consists of 35 exons spanning 27.5 kb. Sequence data for the exon-intron boundaries were determined and examined in the context of topoisomerase IIalpha protein structure comprising three functional domains associated with energy transduction, DNA breakage-reunion activity and nuclear localization. The organization of the 3' half of human TOP2beta, including sequence specifying the C-terminal nuclear localization domain, was also elucidated. Of the 15 introns identified in this 20 kb region of TOP2beta, the first nine and the last intron align in identical positions and display the same phases as introns in TOP2alpha. Though their extreme 3' ends differ, the striking conservation suggests the two genes diverged recently in evolutionary terms consistent with a gene duplication event. Access to TOP2alpha and TOP2beta gene structures should aid studies of mutations and gene rearrangements associated with anticancer drug resistance.  (+info)

DNA topoisomerases are enzymes that modify the topological structure of DNA by regulating the number of twists or supercoils in the double helix. There are two main types of DNA topoisomerases: type I and type II.

Type I DNA topoisomerases function by cutting one strand of the DNA duplex, allowing the uncut strand to rotate around the break, and then resealing the break. This process can relieve both positive and negative supercoiling in DNA, as well as introduce single-stranded breaks into the DNA molecule.

Type I topoisomerases are further divided into three subtypes: type IA, type IB, and type IC. These subtypes differ in their mechanism of action and the structure of the active site tyrosine residue that makes the transient break in the DNA strand.

Overall, DNA topoisomerases play a crucial role in many cellular processes involving DNA, including replication, transcription, recombination, and chromosome segregation. Dysregulation of these enzymes has been implicated in various human diseases, including cancer and genetic disorders.

DNA topoisomerases are enzymes that regulate the topological state of DNA during various cellular processes such as replication, transcription, and repair. They do this by introducing temporary breaks in the DNA strands and allowing the strands to rotate around each other, thereby relieving torsional stress and supercoiling. Topoisomerases are classified into two types: type I and type II.

Type II topoisomerases are further divided into two subtypes: type IIA and type IIB. These enzymes function by forming a covalent bond with the DNA strands, cleaving them, and then passing another segment of DNA through the break before resealing the original strands. This process allows for the removal of both positive and negative supercoils from DNA as well as the separation of interlinked circular DNA molecules (catenanes) or knotted DNA structures.

Type II topoisomerases are essential for cell viability, and their dysfunction has been linked to various human diseases, including cancer and neurodegenerative disorders. They have also emerged as important targets for the development of anticancer drugs that inhibit their activity and induce DNA damage leading to cell death. Examples of type II topoisomerase inhibitors include etoposide, doxorubicin, and mitoxantrone.

DNA topoisomerases are enzymes that play a crucial role in the regulation of DNA topology, which refers to the three-dimensional arrangement of the DNA molecule. These enzymes control the number of twists or coils in the DNA helix by creating temporary breaks in the strands and allowing them to rotate around each other, thereby relieving the torsional stress that builds up during processes such as replication and transcription.

There are two main types of DNA topoisomerases: type I and type II. Type I enzymes create a single-stranded break in the DNA helix, while type II enzymes create a double-stranded break. Both types of enzymes can change the linking number (Lk) of the DNA molecule, which is a topological invariant that describes the overall degree of twist in the helix.

Type I topoisomerases are further divided into two subtypes: type IA and type IB. Type IA enzymes, such as topo I from Escherichia coli, create a transient break in one DNA strand and then pass the other strand through the break before resealing it. In contrast, type IB enzymes, such as human topo I, create a covalent bond with the 3'-phosphate end of the broken strand and then pass the 5'-end through the break before rejoining the ends.

Type II topoisomerases are also divided into two subtypes: type IIA and type IIB. Type IIA enzymes, such as bacterial topo IV and eukaryotic topo II, create a double-stranded break in the DNA helix and then pass another segment of double-stranded DNA through the break before resealing it. Type IIB enzymes, such as bacterial topo III and eukaryotic topo IIIα and β, create a double-stranded break and then pass a single strand of DNA through the break before resealing it.

DNA topoisomerases are important targets for cancer chemotherapy because they are essential for cell division and can be inhibited by drugs such as doxorubicin, etoposide, and irinotecan. However, these drugs can also have significant side effects, including cardiotoxicity and myelosuppression. Therefore, there is ongoing research to develop new topoisomerase inhibitors with improved efficacy and safety profiles.

Topoisomerase II inhibitors are a class of anticancer drugs that work by interfering with the enzyme topoisomerase II, which is essential for DNA replication and transcription. These inhibitors bind to the enzyme-DNA complex, preventing the relaxation of supercoiled DNA and causing DNA strand breaks. This results in the accumulation of double-stranded DNA breaks, which can lead to apoptosis (programmed cell death) in rapidly dividing cells, such as cancer cells. Examples of topoisomerase II inhibitors include etoposide, doxorubicin, and mitoxantrone.

Topoisomerase inhibitors are a class of anticancer drugs that work by interfering with the function of topoisomerases, which are enzymes responsible for relaxing supercoiled DNA during processes such as replication and transcription. Topoisomerase I inhibitors selectively bind to and stabilize the cleavage complex formed between topoisomerase I and DNA, preventing the relegation of the broken DNA strand and resulting in DNA damage and cell death. Examples include irinotecan and topotecan. Topoisomerase II inhibitors, on the other hand, bind to and stabilize the cleavage complex formed between topoisomerase II and DNA, leading to double-stranded DNA breaks and cell death. Examples include doxorubicin, etoposide, and mitoxantrone. These drugs are used in the treatment of various types of cancer.

Topoisomerase I inhibitors are a class of anticancer drugs that work by inhibiting the function of topoisomerase I, an enzyme that plays a crucial role in the relaxation and replication of DNA. By inhibiting this enzyme's activity, these drugs interfere with the normal unwinding and separation of DNA strands, leading to DNA damage and ultimately cell death. Topoisomerase I inhibitors are used in the treatment of various types of cancer, including colon, small cell lung, ovarian, and cervical cancers. Examples of topoisomerase I inhibitors include camptothecin, irinotecan, and topotecan.

Superhelical DNA refers to a type of DNA structure that is formed when the double helix is twisted around itself. This occurs due to the presence of negative supercoiling, which results in an overtwisted state that can be described as having a greater number of helical turns than a relaxed circular DNA molecule.

Superhelical DNA is often found in bacterial and viral genomes, where it plays important roles in compacting the genome into a smaller volume and facilitating processes such as replication and transcription. The degree of supercoiling can affect the structure and function of DNA, with varying levels of supercoiling influencing the accessibility of specific regions of the genome to proteins and other regulatory factors.

Superhelical DNA is typically maintained in a stable state by topoisomerase enzymes, which introduce or remove twists in the double helix to regulate its supercoiling level. Changes in supercoiling can have significant consequences for cellular processes, as they can impact the expression of genes and the regulation of chromosome structure and function.

Proscillaridin is a cardiac glycoside, which is a type of substance derived from certain plants and animals that have been used in traditional medicine to treat heart conditions. It specifically comes from the leaves of the Digitalis lanata plant, also known as woolly foxglove or purple foxglove.

Proscillaridin works by inhibiting the sodium-potassium pump in heart muscle cells, which leads to an increase in intracellular calcium levels and a strengthening of heart contractions. This can be beneficial for individuals with congestive heart failure or atrial fibrillation, as it helps improve the efficiency of the heart's pumping ability.

However, proscillaridin also has a narrow therapeutic index, meaning that there is a small difference between an effective dose and a toxic one. Therefore, its use must be carefully monitored by healthcare professionals to avoid potential adverse effects such as arrhythmias or digitalis toxicity.

Amsacrine is a chemotherapeutic agent, which means it is a medication used to treat cancer. It is classified as an antineoplastic drug, and more specifically, as an intercalating agent and a topoisomerase II inhibitor. Amsacrine works by intercalating, or inserting itself, into the DNA of cancer cells, which prevents the DNA from replicating and ultimately leads to the death of the cancer cell. It is primarily used in the treatment of acute myeloid leukemia (AML) and other hematologic malignancies.

The chemical name for Amsacrine is 5-[3-amino-1-(3-aminopropyl)-2-hydroxybut-1-yloxy]-8-chloro-1,4-naphthoquinone. It has a molecular formula of C16H17ClNO5 and a molecular weight of 359.8 g/mol.

Amsacrine is typically administered intravenously, and its use is usually reserved for patients who have not responded to other forms of chemotherapy. It may be used in combination with other anticancer drugs as part of a treatment regimen. As with any chemotherapeutic agent, Amsacrine can have significant side effects, including nausea, vomiting, and hair loss. It can also cause damage to the heart and other organs, so it is important for patients to be closely monitored during treatment.

It's worth noting that while Amsacrine can be an effective treatment for some types of cancer, it is not a cure-all, and its use must be carefully considered in the context of each individual patient's medical history and current health status.

Catenated DNA refers to the linking or interlocking of two or more DNA molecules in a circular form, where the circles are topologically entangled. This occurs during DNA replication when the sister chromatids (identical copies of DNA) are formed and remain interlinked before they are separated during cell division. The term "catenane" is used to describe this interlocking structure. It is important to note that in linear DNA, the term "catenated" does not apply since there is no circular formation.

A catenane is a type of molecular structure composed of two or more interlocked macrocyclic molecules, which are circular molecules that resemble rings. The term "catenane" comes from the Latin word "catena," meaning "chain." In a catenane, the rings are linked together in a chain-like fashion, but they are not chemically bonded to each other. Instead, they are held together by non-covalent interactions such as van der Waals forces or hydrogen bonds.

Catenanes have attracted significant interest from chemists and materials scientists due to their unique properties and potential applications in fields such as molecular machines, sensors, and drug delivery systems. They can be synthesized using various methods, including template-directed synthesis, where a template molecule is used to guide the formation of the interlocked rings.

In summary, catenanes are interlocked molecular structures composed of two or more macrocyclic rings that are held together by non-covalent interactions. They have potential applications in various fields and can be synthesized using different methods.

DNA gyrase is a type II topoisomerase enzyme that plays a crucial role in the negative supercoiling and relaxation of DNA in bacteria. It functions by introducing transient double-stranded breaks into the DNA helix, allowing the strands to pass through one another and thereby reducing positive supercoils or introducing negative supercoils as required for proper DNA function, replication, and transcription.

DNA gyrase is composed of two subunits, GyrA and GyrB, which form a heterotetrameric structure (AB-BA) in the functional enzyme. The enzyme's activity is targeted by several antibiotics, such as fluoroquinolones and novobiocin, making it an essential target for antibacterial drug development.

In summary, DNA gyrase is a bacterial topoisomerase responsible for maintaining the correct supercoiling of DNA during replication and transcription, which can be inhibited by specific antibiotics to combat bacterial infections.

DNA Topoisomerase IV is a type of enzyme that plays a crucial role in the relaxation and manipulation of supercoiled DNA during processes such as replication, transcription, and chromosome segregation. It functions by temporarily cleaving and rejoining the DNA strands to allow for the unlinking and separation of DNA molecules. This enzyme primarily targets double-stranded DNA and is especially important in bacteria, where it helps to resolve the topological challenges that arise during DNA replication and segregation of daughter chromosomes during cell division. Inhibition of DNA Topoisomerase IV has been explored as a strategy for developing antibacterial drugs, as this enzyme is essential for bacterial survival and is not found in humans.

Teniposide is a synthetic podophyllotoxin derivative, which is an antineoplastic agent. It works by interfering with the DNA synthesis and function of cancer cells, leading to cell cycle arrest and apoptosis (programmed cell death). Teniposide is primarily used in the treatment of acute lymphoblastic leukemia (ALL) and other malignancies in children. It is often administered through intravenous infusion and is typically used in combination with other chemotherapeutic agents.

The medical definition of Teniposide can be stated as:

Teniposide, chemically known as (4'-demethylepipodophyllotoxin 9-[4,6-O-(R)-benzylidene-α-L-glucopyranoside]), is a semi-synthetic podophyllotoxin derivative with antineoplastic activity. It inhibits DNA topoisomerase II, leading to the formation of DNA-topoisomerase II cleavable complexes, G2 arrest, and apoptosis in cancer cells. Teniposide is primarily used in the treatment of acute lymphoblastic leukemia (ALL) and other malignancies in children, often administered through intravenous infusion and typically used in combination with other chemotherapeutic agents.

Novobiocin is an antibiotic derived from the actinomycete species Streptomyces niveus. It belongs to the class of drugs known as aminocoumarins, which function by inhibiting bacterial DNA gyrase, thereby preventing DNA replication and transcription. Novobiocin has activity against a narrow range of gram-positive bacteria, including some strains of Staphylococcus aureus (particularly those resistant to penicillin and methicillin), Streptococcus pneumoniae, and certain mycobacteria. It is used primarily in the treatment of serious staphylococcal infections and is administered orally or intravenously.

It's important to note that Novobiocin has been largely replaced by other antibiotics due to its narrow spectrum of activity, potential for drug interactions, and adverse effects. It is not widely used in clinical practice today.

Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.

Nucleic acid conformation refers to the three-dimensional structure that nucleic acids (DNA and RNA) adopt as a result of the bonding patterns between the atoms within the molecule. The primary structure of nucleic acids is determined by the sequence of nucleotides, while the conformation is influenced by factors such as the sugar-phosphate backbone, base stacking, and hydrogen bonding.

Two common conformations of DNA are the B-form and the A-form. The B-form is a right-handed helix with a diameter of about 20 Å and a pitch of 34 Å, while the A-form has a smaller diameter (about 18 Å) and a shorter pitch (about 25 Å). RNA typically adopts an A-form conformation.

The conformation of nucleic acids can have significant implications for their function, as it can affect their ability to interact with other molecules such as proteins or drugs. Understanding the conformational properties of nucleic acids is therefore an important area of research in molecular biology and medicine.

'Escherichia coli' (E. coli) is a type of gram-negative, facultatively anaerobic, rod-shaped bacterium that commonly inhabits the intestinal tract of humans and warm-blooded animals. It is a member of the family Enterobacteriaceae and one of the most well-studied prokaryotic model organisms in molecular biology.

While most E. coli strains are harmless and even beneficial to their hosts, some serotypes can cause various forms of gastrointestinal and extraintestinal illnesses in humans and animals. These pathogenic strains possess virulence factors that enable them to colonize and damage host tissues, leading to diseases such as diarrhea, urinary tract infections, pneumonia, and sepsis.

E. coli is a versatile organism with remarkable genetic diversity, which allows it to adapt to various environmental niches. It can be found in water, soil, food, and various man-made environments, making it an essential indicator of fecal contamination and a common cause of foodborne illnesses. The study of E. coli has contributed significantly to our understanding of fundamental biological processes, including DNA replication, gene regulation, and protein synthesis.

Camptothecin is a topoisomerase I inhibitor, which is a type of chemotherapeutic agent used in cancer treatment. It works by interfering with the function of an enzyme called topoisomerase I, which helps to uncoil DNA during cell division. By inhibiting this enzyme, camptothecin prevents the cancer cells from dividing and growing, ultimately leading to their death.

Camptothecin is found naturally in the bark and stem of the Camptotheca acuminata tree, also known as the "happy tree," which is native to China. It was first isolated in 1966 and has since been developed into several synthetic derivatives, including irinotecan and topotecan, which are used clinically to treat various types of cancer, such as colon, lung, and ovarian cancers.

Like other chemotherapeutic agents, camptothecin can have significant side effects, including nausea, vomiting, diarrhea, and myelosuppression (suppression of bone marrow function). It is important for patients receiving camptothecin-based therapies to be closely monitored by their healthcare team to manage these side effects effectively.

Eukaryotic cells are complex cells that characterize the cells of all living organisms except bacteria and archaea. They are typically larger than prokaryotic cells and contain a true nucleus and other membrane-bound organelles. The nucleus houses the genetic material, DNA, which is organized into chromosomes. Other organelles include mitochondria, responsible for energy production; chloroplasts, present in plant cells and responsible for photosynthesis; endoplasmic reticulum, involved in protein synthesis; Golgi apparatus, involved in the processing and transport of proteins and lipids; lysosomes, involved in digestion and waste disposal; and vacuoles, involved in storage and waste management. Eukaryotic cells also have a cytoskeleton made up of microtubules, intermediate filaments, and actin filaments that provide structure, support, and mobility to the cell.

Circular DNA is a type of DNA molecule that forms a closed loop, rather than the linear double helix structure commonly associated with DNA. This type of DNA is found in some viruses, plasmids (small extrachromosomal DNA molecules found in bacteria), and mitochondria and chloroplasts (organelles found in plant and animal cells).

Circular DNA is characterized by the absence of telomeres, which are the protective caps found on linear chromosomes. Instead, circular DNA has a specific sequence where the two ends join together, known as the origin of replication and the replication terminus. This structure allows for the DNA to be replicated efficiently and compactly within the cell.

Because of its circular nature, circular DNA is more resistant to degradation by enzymes that cut linear DNA, making it more stable in certain environments. Additionally, the ability to easily manipulate and clone circular DNA has made it a valuable tool in molecular biology and genetic engineering.

Molecular models are three-dimensional representations of molecular structures that are used in the field of molecular biology and chemistry to visualize and understand the spatial arrangement of atoms and bonds within a molecule. These models can be physical or computer-generated and allow researchers to study the shape, size, and behavior of molecules, which is crucial for understanding their function and interactions with other molecules.

Physical molecular models are often made up of balls (representing atoms) connected by rods or sticks (representing bonds). These models can be constructed manually using materials such as plastic or wooden balls and rods, or they can be created using 3D printing technology.

Computer-generated molecular models, on the other hand, are created using specialized software that allows researchers to visualize and manipulate molecular structures in three dimensions. These models can be used to simulate molecular interactions, predict molecular behavior, and design new drugs or chemicals with specific properties. Overall, molecular models play a critical role in advancing our understanding of molecular structures and their functions.

A plasmid is a small, circular, double-stranded DNA molecule that is separate from the chromosomal DNA of a bacterium or other organism. Plasmids are typically not essential for the survival of the organism, but they can confer beneficial traits such as antibiotic resistance or the ability to degrade certain types of pollutants.

Plasmids are capable of replicating independently of the chromosomal DNA and can be transferred between bacteria through a process called conjugation. They often contain genes that provide resistance to antibiotics, heavy metals, and other environmental stressors. Plasmids have also been engineered for use in molecular biology as cloning vectors, allowing scientists to replicate and manipulate specific DNA sequences.

Plasmids are important tools in genetic engineering and biotechnology because they can be easily manipulated and transferred between organisms. They have been used to produce vaccines, diagnostic tests, and genetically modified organisms (GMOs) for various applications, including agriculture, medicine, and industry.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

DNA replication is the biological process by which DNA makes an identical copy of itself during cell division. It is a fundamental mechanism that allows genetic information to be passed down from one generation of cells to the next. During DNA replication, each strand of the double helix serves as a template for the synthesis of a new complementary strand. This results in the creation of two identical DNA molecules. The enzymes responsible for DNA replication include helicase, which unwinds the double helix, and polymerase, which adds nucleotides to the growing strands.

Catalysis is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst, which remains unchanged at the end of the reaction. A catalyst lowers the activation energy required for the reaction to occur, thereby allowing the reaction to proceed more quickly and efficiently. This can be particularly important in biological systems, where enzymes act as catalysts to speed up metabolic reactions that are essential for life.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

DNA damage refers to any alteration in the structure or composition of deoxyribonucleic acid (DNA), which is the genetic material present in cells. DNA damage can result from various internal and external factors, including environmental exposures such as ultraviolet radiation, tobacco smoke, and certain chemicals, as well as normal cellular processes such as replication and oxidative metabolism.

Examples of DNA damage include base modifications, base deletions or insertions, single-strand breaks, double-strand breaks, and crosslinks between the two strands of the DNA helix. These types of damage can lead to mutations, genomic instability, and chromosomal aberrations, which can contribute to the development of diseases such as cancer, neurodegenerative disorders, and aging-related conditions.

The body has several mechanisms for repairing DNA damage, including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. However, if the damage is too extensive or the repair mechanisms are impaired, the cell may undergo apoptosis (programmed cell death) to prevent the propagation of potentially harmful mutations.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

"Saccharomyces cerevisiae" is not typically considered a medical term, but it is a scientific name used in the field of microbiology. It refers to a species of yeast that is commonly used in various industrial processes, such as baking and brewing. It's also widely used in scientific research due to its genetic tractability and eukaryotic cellular organization.

However, it does have some relevance to medical fields like medicine and nutrition. For example, certain strains of S. cerevisiae are used as probiotics, which can provide health benefits when consumed. They may help support gut health, enhance the immune system, and even assist in the digestion of certain nutrients.

In summary, "Saccharomyces cerevisiae" is a species of yeast with various industrial and potential medical applications.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Bacterial DNA refers to the genetic material found in bacteria. It is composed of a double-stranded helix containing four nucleotide bases - adenine (A), thymine (T), guanine (G), and cytosine (C) - that are linked together by phosphodiester bonds. The sequence of these bases in the DNA molecule carries the genetic information necessary for the growth, development, and reproduction of bacteria.

Bacterial DNA is circular in most bacterial species, although some have linear chromosomes. In addition to the main chromosome, many bacteria also contain small circular pieces of DNA called plasmids that can carry additional genes and provide resistance to antibiotics or other environmental stressors.

Unlike eukaryotic cells, which have their DNA enclosed within a nucleus, bacterial DNA is present in the cytoplasm of the cell, where it is in direct contact with the cell's metabolic machinery. This allows for rapid gene expression and regulation in response to changing environmental conditions.

DNA cleavage is the breaking of the phosphodiester bonds in the DNA molecule, resulting in the separation of the two strands of the double helix. This process can occur through chemical or enzymatic reactions and can result in various types of damage to the DNA molecule, including single-strand breaks, double-strand breaks, and base modifications.

Enzymatic DNA cleavage is typically carried out by endonucleases, which are enzymes that cut DNA molecules at specific sequences or structures. There are two main types of endonucleases: restriction endonucleases and repair endonucleases. Restriction endonucleases recognize and cleave specific DNA sequences, often used in molecular biology techniques such as genetic engineering and cloning. Repair endonucleases, on the other hand, are involved in DNA repair processes and recognize and cleave damaged or abnormal DNA structures.

Chemical DNA cleavage can occur through various mechanisms, including oxidation, alkylation, or hydrolysis of the phosphodiester bonds. Chemical agents such as hydrogen peroxide, formaldehyde, or hydrazine can induce chemical DNA cleavage and are often used in laboratory settings for various purposes, such as DNA fragmentation or labeling.

Overall, DNA cleavage is an essential process in many biological functions, including DNA replication, repair, and recombination. However, excessive or improper DNA cleavage can lead to genomic instability, mutations, and cell death.

Antineoplastic agents are a class of drugs used to treat malignant neoplasms or cancer. These agents work by inhibiting the growth and proliferation of cancer cells, either by killing them or preventing their division and replication. Antineoplastic agents can be classified based on their mechanism of action, such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, and targeted therapy agents.

Alkylating agents work by adding alkyl groups to DNA, which can cause cross-linking of DNA strands and ultimately lead to cell death. Antimetabolites interfere with the metabolic processes necessary for DNA synthesis and replication, while topoisomerase inhibitors prevent the relaxation of supercoiled DNA during replication. Mitotic inhibitors disrupt the normal functioning of the mitotic spindle, which is essential for cell division. Targeted therapy agents are designed to target specific molecular abnormalities in cancer cells, such as mutated oncogenes or dysregulated signaling pathways.

It's important to note that antineoplastic agents can also affect normal cells and tissues, leading to various side effects such as nausea, vomiting, hair loss, and myelosuppression (suppression of bone marrow function). Therefore, the use of these drugs requires careful monitoring and management of their potential adverse effects.

Adenosine Triphosphate (ATP) is a high-energy molecule that stores and transports energy within cells. It is the main source of energy for most cellular processes, including muscle contraction, nerve impulse transmission, and protein synthesis. ATP is composed of a base (adenine), a sugar (ribose), and three phosphate groups. The bonds between these phosphate groups contain a significant amount of energy, which can be released when the bond between the second and third phosphate group is broken, resulting in the formation of adenosine diphosphate (ADP) and inorganic phosphate. This process is known as hydrolysis and can be catalyzed by various enzymes to drive a wide range of cellular functions. ATP can also be regenerated from ADP through various metabolic pathways, such as oxidative phosphorylation or substrate-level phosphorylation, allowing for the continuous supply of energy to cells.

Ellipticines are a class of naturally occurring alkaloids that have been isolated from various plants, including those in the family Apocynaceae. These compounds have been found to exhibit various biological activities, including anti-cancer and anti-microbial properties.

Ellipticines have a unique chemical structure, characterized by a planar, aromatic core with two side chains that contain nitrogen atoms. This structure allows ellipticines to intercalate into DNA, disrupting its normal function and leading to cell death. As a result, ellipticines have been studied as potential anti-cancer agents, particularly for the treatment of drug-resistant cancers.

In addition to their anti-cancer properties, ellipticines have also been found to exhibit antibacterial, antifungal, and antiparasitic activities. However, further research is needed to fully understand the mechanisms behind these effects and to determine the safety and efficacy of ellipticines as therapeutic agents.

Collagen Type II is a specific type of collagen that is a major component of the extracellular matrix in articular cartilage, which is the connective tissue that covers and protects the ends of bones in joints. It is also found in other tissues such as the vitreous humor of the eye and the inner ear.

Collagen Type II is a triple helix molecule composed of three polypeptide chains that contain a high proportion of the amino acids proline and hydroxyproline. This type of collagen provides structural support and elasticity to tissues, and it also plays a role in the regulation of cell behavior and signaling.

Collagen Type II is a target for autoimmune responses in conditions such as rheumatoid arthritis, where the immune system mistakenly attacks the body's own collagen, leading to joint inflammation and damage. It is also a common component of various dietary supplements and therapies used to support joint health and treat osteoarthritis.

Aminoacridines are a group of synthetic chemical compounds that contain an acridine nucleus, which is a tricyclic aromatic structure, substituted with one or more amino groups. These compounds have been studied for their potential therapeutic properties, particularly as antiseptics and antibacterial agents. However, their use in medicine has declined due to the development of newer and safer antibiotics. Some aminoacridines also exhibit antimalarial, antifungal, and antiviral activities. They can intercalate into DNA, disrupting its structure and function, which is thought to contribute to their antimicrobial effects. However, this property also makes them potentially mutagenic and carcinogenic, limiting their clinical use.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Quinolones are a class of antibacterial agents that are widely used in medicine to treat various types of infections caused by susceptible bacteria. These synthetic drugs contain a chemical structure related to quinoline and have broad-spectrum activity against both Gram-positive and Gram-negative bacteria. Quinolones work by inhibiting the bacterial DNA gyrase or topoisomerase IV enzymes, which are essential for bacterial DNA replication, transcription, and repair.

The first quinolone antibiotic was nalidixic acid, discovered in 1962. Since then, several generations of quinolones have been developed, with each generation having improved antibacterial activity and a broader spectrum of action compared to the previous one. The various generations of quinolones include:

1. First-generation quinolones (e.g., nalidixic acid): Primarily used for treating urinary tract infections caused by Gram-negative bacteria.
2. Second-generation quinolones (e.g., ciprofloxacin, ofloxacin, norfloxacin): These drugs have improved activity against both Gram-positive and Gram-negative bacteria and are used to treat a wider range of infections, including respiratory, gastrointestinal, and skin infections.
3. Third-generation quinolones (e.g., levofloxacin, sparfloxacin, grepafloxacin): These drugs have enhanced activity against Gram-positive bacteria, including some anaerobes and atypical organisms like Legionella and Mycoplasma species.
4. Fourth-generation quinolones (e.g., moxifloxacin, gatifloxacin): These drugs have the broadest spectrum of activity, including enhanced activity against Gram-positive bacteria, anaerobes, and some methicillin-resistant Staphylococcus aureus (MRSA) strains.

Quinolones are generally well-tolerated, but like all medications, they can have side effects. Common adverse reactions include gastrointestinal symptoms (nausea, vomiting, diarrhea), headache, and dizziness. Serious side effects, such as tendinitis, tendon rupture, peripheral neuropathy, and QT interval prolongation, are less common but can occur, particularly in older patients or those with underlying medical conditions. The use of quinolones should be avoided or used cautiously in these populations.

Quinolone resistance has become an increasing concern due to the widespread use of these antibiotics. Bacteria can develop resistance through various mechanisms, including chromosomal mutations and the acquisition of plasmid-mediated quinolone resistance genes. The overuse and misuse of quinolones contribute to the emergence and spread of resistant strains, which can limit treatment options for severe infections caused by these bacteria. Therefore, it is essential to use quinolones judiciously and only when clinically indicated, to help preserve their effectiveness and prevent further resistance development.

Crithidia is a genus of protozoan parasites belonging to the family Trypanosomatidae. These parasites are primarily found in the digestive tracts of insects, particularly blood-sucking insects such as mosquitoes and reduviid bugs. They are transmitted to the insect through the ingestion of infected prey, such as other insects.

Crithidia species are closely related to Trypanosoma species, which can cause serious diseases in humans and animals, such as sleeping sickness and Chagas disease. However, Crithidia species are not typically considered to be human pathogens, although there have been rare cases of human infection reported in the literature.

In general, Crithidia species are studied for their potential use as model organisms in research on topics such as evolution, genetics, and cell biology. They are also used in forensic entomology to help estimate the postmortem interval (PMI) in cases of insect-associated death investigations.

Fluoroquinolones are a class of antibiotics that are widely used to treat various types of bacterial infections. They work by interfering with the bacteria's ability to replicate its DNA, which ultimately leads to the death of the bacterial cells. Fluoroquinolones are known for their broad-spectrum activity against both gram-positive and gram-negative bacteria.

Some common fluoroquinolones include ciprofloxacin, levofloxacin, moxifloxacin, and ofloxacin. These antibiotics are often used to treat respiratory infections, urinary tract infections, skin infections, and gastrointestinal infections, among others.

While fluoroquinolones are generally well-tolerated, they can cause serious side effects in some people, including tendonitis, nerve damage, and changes in mood or behavior. As with all antibiotics, it's important to use fluoroquinolones only when necessary and under the guidance of a healthcare provider.

The kinetoplast is a unique structure found in the single, mitochondrion of certain protozoan parasites, including those of the genera Trypanosoma and Leishmania. It consists of a network of circular DNA molecules that are highly concentrated and tightly packed. These DNA molecules contain genetic information necessary for the functioning of the unique mitochondrion in these organisms.

The kinetoplast DNA (kDNA) is organized into thousands of maxicircles and minicircles, which vary in size and number depending on the species. Maxicircles are similar to mammalian mitochondrial DNA and encode proteins involved in oxidative phosphorylation, while minicircles contain sequences that code for guide RNAs involved in the editing of maxicircle transcripts.

The kDNA undergoes dynamic rearrangements during the life cycle of these parasites, which involves different morphological and metabolic forms. The study of kDNA has provided valuable insights into the biology and evolution of these important pathogens and has contributed to the development of novel therapeutic strategies.

Aminocoumarins are a class of antibiotics that inhibit bacterial DNA gyrase, an enzyme necessary for DNA replication and transcription. These antibiotics have a coumarin nucleus with an attached amino group. The most well-known aminocoumarin is novobiocin, which is used to treat various bacterial infections. However, the use of aminocoumarins has become limited due to the emergence of bacterial resistance and the availability of other more effective antibiotics.

Intercalating agents are chemical substances that can be inserted between the stacked bases of DNA, creating a separation or "intercalation" of the base pairs. This property is often exploited in cancer chemotherapy, where intercalating agents like doxorubicin and daunorubicin are used to inhibit the replication and transcription of cancer cells by preventing the normal functioning of their DNA. However, these agents can also have toxic effects on normal cells, particularly those that divide rapidly, such as bone marrow and gut epithelial cells. Therefore, their use must be carefully monitored and balanced against their therapeutic benefits.

Anti-infective agents are a class of medications that are used to treat infections caused by various microorganisms such as bacteria, viruses, fungi, and parasites. These agents work by either killing the microorganism or inhibiting its growth, thereby helping to control the infection and alleviate symptoms.

There are several types of anti-infective agents, including:

1. Antibiotics: These are medications that are used to treat bacterial infections. They work by either killing bacteria (bactericidal) or inhibiting their growth (bacteriostatic).
2. Antivirals: These are medications that are used to treat viral infections. They work by interfering with the replication of the virus, preventing it from spreading and causing further damage.
3. Antifungals: These are medications that are used to treat fungal infections. They work by disrupting the cell membrane of the fungus, killing it or inhibiting its growth.
4. Antiparasitics: These are medications that are used to treat parasitic infections. They work by either killing the parasite or inhibiting its growth and reproduction.

It is important to note that anti-infective agents are not effective against all types of infections, and it is essential to use them appropriately to avoid the development of drug-resistant strains of microorganisms.

Etoposide is a chemotherapy medication used to treat various types of cancer, including lung cancer, testicular cancer, and certain types of leukemia. It works by inhibiting the activity of an enzyme called topoisomerase II, which is involved in DNA replication and transcription. By doing so, etoposide can interfere with the growth and multiplication of cancer cells.

Etoposide is often administered intravenously in a hospital or clinic setting, although it may also be given orally in some cases. The medication can cause a range of side effects, including nausea, vomiting, hair loss, and an increased risk of infection. It can also have more serious side effects, such as bone marrow suppression, which can lead to anemia, bleeding, and a weakened immune system.

Like all chemotherapy drugs, etoposide is not without risks and should only be used under the close supervision of a qualified healthcare provider. It is important for patients to discuss the potential benefits and risks of this medication with their doctor before starting treatment.

Naphthyridines are a class of heterocyclic organic compounds that contain a naphthyridine core structure, which is a polycyclic aromatic hydrocarbon made up of two benzene rings fused to a tetrahydropyridine ring. They have a variety of pharmacological activities and are used in the development of various therapeutic agents, including antibiotics, antivirals, and anticancer drugs.

In medical terms, naphthyridines do not have a specific clinical definition or application, but they are rather a chemical class that is utilized in the design and synthesis of drugs with potential therapeutic benefits. The unique structure and properties of naphthyridines make them attractive candidates for drug development, particularly in areas where new treatments are needed to overcome drug resistance or improve efficacy.

It's worth noting that while naphthyridines have shown promise in preclinical studies, further research is needed to fully understand their safety and effectiveness in humans before they can be approved as therapeutic agents.

Neoplasm antigens, also known as tumor antigens, are substances that are produced by cancer cells (neoplasms) and can stimulate an immune response. These antigens can be proteins, carbohydrates, or other molecules that are either unique to the cancer cells or are overexpressed or mutated versions of normal cellular proteins.

Neoplasm antigens can be classified into two main categories: tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs). TSAs are unique to cancer cells and are not expressed by normal cells, while TAAs are present at low levels in normal cells but are overexpressed or altered in cancer cells.

TSAs can be further divided into viral antigens and mutated antigens. Viral antigens are produced when cancer is caused by a virus, such as human papillomavirus (HPV) in cervical cancer. Mutated antigens are the result of genetic mutations that occur during cancer development and are unique to each patient's tumor.

Neoplasm antigens play an important role in the immune response against cancer. They can be recognized by the immune system, leading to the activation of immune cells such as T cells and natural killer (NK) cells, which can then attack and destroy cancer cells. However, cancer cells often develop mechanisms to evade the immune response, allowing them to continue growing and spreading.

Understanding neoplasm antigens is important for the development of cancer immunotherapies, which aim to enhance the body's natural immune response against cancer. These therapies include checkpoint inhibitors, which block proteins that inhibit T cell activation, and therapeutic vaccines, which stimulate an immune response against specific tumor antigens.

I'm sorry for any confusion, but "Indenes" is not a recognized medical term or concept in the field of medicine or healthcare. It may be that there is a spelling mistake or typo in your question. If you are referring to "Indenes" as a chemical compound, it is a polycyclic aromatic hydrocarbon (PAH) with the molecular formula C9H8. However, I would recommend consulting a chemistry or toxicology resource for information on its non-medical uses and properties.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Recombinases are enzymes that catalyze the process of recombination between two or more DNA molecules by breaking and rejoining their strands. They play a crucial role in various biological processes such as DNA repair, genetic recombination during meiosis, and site-specific genetic modifications.

Recombinases recognize and bind to specific DNA sequences, called recognition sites or crossover sites, where they cleave the phosphodiester bonds of the DNA backbone, forming a Holliday junction intermediate. The recombinase then catalyzes the exchange of strands between the two DNA molecules at the junction and subsequently ligates the broken ends to form new phosphodiester bonds, resulting in the recombination of the DNA molecules.

There are several types of recombinases, including serine recombinases, tyrosine recombinases, and lambda integrase. These enzymes differ in their recognition sites, catalytic mechanisms, and biological functions. Recombinases have important applications in molecular biology and genetic engineering, such as generating targeted DNA deletions or insertions, constructing genetic circuits, and developing gene therapy strategies.

4-Quinolones are a class of antibacterial agents that are chemically characterized by a 4-oxo-1,4-dihydroquinoline ring. They include drugs such as ciprofloxacin, levofloxacin, and moxifloxacin, among others. These antibiotics work by inhibiting the bacterial DNA gyrase or topoisomerase IV enzymes, which are essential for bacterial DNA replication, transcription, repair, and recombination. This leads to bacterial cell death.

4-Quinolones have a broad spectrum of activity against both Gram-positive and Gram-negative bacteria and are used to treat a variety of infections, including urinary tract infections, pneumonia, skin and soft tissue infections, and intra-abdominal infections. However, the use of 4-quinolones is associated with an increased risk of tendinitis and tendon rupture, as well as other serious adverse effects such as peripheral neuropathy, QT interval prolongation, and aortic aneurysm and dissection. Therefore, their use should be restricted to situations where the benefits outweigh the risks.

"Sulfolobus" is a genus of archaea, which are single-celled microorganisms that share characteristics with both bacteria and eukaryotes. These archaea are extremophiles, meaning they thrive in extreme environments that are hostile to most other life forms. Specifically, Sulfolobus species are acidothermophiles, capable of growing at temperatures between 75-85°C and pH levels near 3. They are commonly found in volcanic hot springs and other acidic, high-temperature environments. The cells of Sulfolobus are typically irregular in shape and have a unique system for replicating their DNA. Some species are capable of oxidizing sulfur compounds as a source of energy.

Electrophoresis, Agar Gel is a laboratory technique used to separate and analyze DNA, RNA, or proteins based on their size and electrical charge. In this method, the sample is mixed with agarose gel, a gelatinous substance derived from seaweed, and then solidified in a horizontal slab-like format. An electric field is applied to the gel, causing the negatively charged DNA or RNA molecules to migrate towards the positive electrode. The smaller molecules move faster through the gel than the larger ones, resulting in their separation based on size. This technique is widely used in molecular biology and genetics research, as well as in diagnostic testing for various genetic disorders.

Triterpenes are a type of natural compound that are composed of six isoprene units and have the molecular formula C30H48. They are synthesized through the mevalonate pathway in plants, fungi, and some insects, and can be found in a wide variety of natural sources, including fruits, vegetables, and medicinal plants.

Triterpenes have diverse structures and biological activities, including anti-inflammatory, antiviral, and cytotoxic effects. Some triterpenes are also used in traditional medicine, such as glycyrrhizin from licorice root and betulinic acid from the bark of birch trees.

Triterpenes can be further classified into various subgroups based on their carbon skeletons, including squalene, lanostane, dammarane, and ursane derivatives. Some triterpenes are also modified through various biochemical reactions to form saponins, steroids, and other compounds with important biological activities.

Watt PM, Hickson ID (November 1994). "Structure and function of type II DNA topoisomerases". The Biochemical Journal. 303 (Pt 3 ... DNA topoisomerase IIα is a human enzyme encoded by the TOP2A gene. Topoisomerase IIα relieves topological DNA stress during ... Topoisomerase II TOP2B - Topoisomerase II beta Gene duplication Ataxia-telangiectasia TOPBP1 GRCh38: Ensembl release 89: ... "Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa". Emanuelli A, Borroni AP, Apel-Sarid L, Shah PA, Ayyathan DM, Koganti P ...
There are two subclasses of type II topoisomerases, type IIA and IIB. Type IIA topoisomerases include the enzymes DNA gyrase, ... Wikimedia Commons has media related to Type II DNA topoisomerase. DNA+Topoisomerases,+Type+II at the U.S. National Library of ... type II topoisomerases are needed for the same reason. Small molecules that target type II topoisomerase are divided into two ... type IIA topoisomerases are able to simplify DNA topology, while type IIB topoisomerases do not. Type IIA topoisomerases ...
... is one of two Type II topoisomerases in bacteria, the other being DNA gyrase. Like gyrase, topoisomerase IV is ... Topoisomerase IV has two functions in the cell. First, it is responsible for unlinking, or decatenating, DNA following DNA ... Wikimedia Commons has media related to DNA topoisomerase IV. DNA+Topoisomerase+IV at the U.S. National Library of Medicine ... DNA gyrases are analogous enzymes in other organisms. While topoisomerase IV does relax positive supercoils like DNA gyrase, it ...
Her research considers the structure-function properties of DNA and DNA topoisomerases. DNA topisomerases are enzymes that ... Catalytic mechanism of eukaryotic topoisomerase II (Thesis). OCLC 24362089. "E. Lynn Zechiedrich, Ph.D." "Baylor researchers ... Zechiedrich's laboratory has focused on better understanding fluoroquinolones, broad-spectrum antibiotics that target type-2 ... Her laboratory's research considers the structure-function properties of DNA and DNA topoisomerases. She was elected to the ...
... , or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that ... Huang, Wai Mun (1986). "Nucleotide sequence of a type II DNA topoisomerase gene. Bacteriophage T4 gene 39". Nucleic Acids ... This process occurs in bacteria, whose single circular DNA is cut by DNA gyrase and the two ends are then twisted around each ... As the result of a catalytic cycle two ATP molecules are hydrolyzed and two negative supercoils are introduced into the DNA ...
It functions by inhibiting two bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. Topoisomerase IV is an enzyme ... Drlica K, Zhao X (September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiology and Molecular Biology ... Two deaths were observed in the levofloxacin group, neither of which was thought to be treatment-related. Spontaneous reports ... It works by interfering with the bacterium's DNA. Ofloxacin was patented in 1980 and approved for medical use in 1985. It is on ...
DNA topology Supercoil Type I topoisomerase Type II topoisomerase Topoisomerase I Topoisomerase IIα Topoisomerase IIβ ... type I topoisomerases) or both (type II topoisomerases) of the DNA strands. This transient break allows the DNA to be untangled ... At least one topoisomerase, DNA topoisomerase II beta (topo IIβ), has a regulatory role in gene transcription. Topo IIβ- ... However, the type II enzymes, DNA gyrase and DNA topoisomerase IV, have enjoyed enormous success as targets for the widely-used ...
The gyrB gene, subunit B protein, is a type II topoisomerase that is essential for DNA replication. This gene is conserved ... DNA gyrase is made of two subunits, A and B. These subunits are denoted as gyrA and gyrB. ... DNA gyrase is an important enzyme that introduces a negative supercoil to the DNA and is responsible for the biological ... B. safensis type strain at BacDive B. safensis type strain at NamesforLife.com (Articles with short description, Short ...
Topoisomerases such as DNA gyrase (Type II Topoisomerase) play a role in relieving some of the stress during DNA/RNA synthesis ... Supercoiled DNA forms two structures; a plectoneme or a toroid, or a combination of both. A negatively supercoiled DNA molecule ... The linking number is the most descriptive property of supercoiled DNA. Lko, the number of turns in the relaxed (B type) DNA ... DNA supercoiling is important for DNA packaging within all cells. Because the length of DNA can be thousands of times that of a ...
... it functions by inhibiting the DNA gyrase and topoisomerase IV, two bacterial type IIA topoisomerases. Topoisomerase IV is ... DNA gyrase, on the other hand, is responsible for supercoiling the DNA, so that it will fit in the newly formed cells. Both ... Drlica K, Zhao X (1 September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiol Mol Biol Rev. 61 (3): 377- ... This enantiomer binds more effectively to the DNA gyrase enzyme and to topoisomerase IV than its (+)-(R)-counterpart. ...
... like other fluoroquinolones is derived from its activity against type II topoisomerases DNA gyrase and topoisomerase IV. ... reactive oxygen species that can damage cellular structures-including DNA. For this reason clinafloxacin can also be classified ... It is soluble in methanol (about 2 mg/mL at 25 °C) and water. In the 1990s, clinafloxacin showed promise as a novel, broad- ... 58 Suppl 2: 60-4. doi:10.2165/00003495-199958002-00012. PMID 10553708. S2CID 9396114. "Clinafloxacin Hydrochloride (CAS 105956- ...
It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, enzymes necessary to separate bacterial ... Drlica K, Zhao X (September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiology and Molecular Biology ... Norfloxacin does not bind to DNA gyrase but does bind to the substrate DNA. A review in 2001 suggests that cytotoxicity of ... conversion of the topoisomerase-quinolone-DNA complex to an irreversible form and (2) generation of a double-strand break by ...
It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, enzymes necessary to separate bacterial ... Drlica K, Zhao X (September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiology and Molecular Biology ... In 2007, the U.S. District Court for the District of Delaware held that two Bayer patents on Avelox are valid and enforceable, ... However, this patent was extended for an additional two and one half years on 16 September 2004, and as such was not expected ...
It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, enzymes necessary to separate bacterial ... "Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase alpha primase complex, topoisomerases I and II, and growth ... Identification of topoisomerase II as the primary cellular target for the quinolone CP-115,953 in yeast". The Journal of ... feature of drugs based on the quinolone structure is their remarkable ability to target different type II topoisomerase enzymes ...
... they inhibit the ligase activity of the type II topoisomerases, DNA gyrase and topoisomerase IV, which cut DNA to introduce ... Identification of topoisomerase II as the primary cellular target for the quinolone CP-115,953 in yeast" (PDF). The Journal of ... For many Gram-negative bacteria, DNA gyrase is the target, whereas topoisomerase IV is the target for many Gram-positive ... Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing ...
DNA polymerases, and Type II topoisomerases. Much research has been done in the years subsequent to this discovery and it has ... various DNA repair mechanisms, RNA transcription and DNA replication. DNA can have mutations that cause a base in the DNA ... There are two mechanisms of DNA base flipping: active and passive. In the active mechanism, an enzyme binds to the DNA and then ... DNA repair Base excision repair DNA replication RNA transcription DNA methylation DNA methyltransferase Genetic recombination ...
It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, which is an enzyme necessary to separate ... Drlica K, Zhao X (1 September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiol Mol Biol Rev. 61 (3): 377- ... replicated DNA, thereby inhibiting cell division. Tendinitis and rupture, usually of the Achilles tendon, are class-effects of ...
... contrary to the typical negative supercoils introduced by the type II topoisomerase DNA gyrase. These positive supercoils can ... Reverse gyrase is a type I topoisomerase that introduces positive supercoils into DNA, ... reverse gyrase can only cleave single stranded DNA. More specifically, reverse gyrase is a member of the type IA topoisomerase ... type IA enzymes also tend to have RNA-topoisomerase activities. These RNA topoisomerases help keep longer RNA strands from ...
DNA Topoisomerase II Beta (TOP2B) activity is essential for the expression of IEGs in a type of learning experience in mice ... June 2019). "Release of paused RNA polymerase II at specific loci favors DNA double-strand-break formation and promotes cancer ... This type of memory cannot be prolonged via rehearsal. Three types of sensory memories exist. Iconic memory is a fast decaying ... and DNA LIGASE IV) (see Figure). These enzymes repair the double-strand breaks within about 15 minutes to two hours. The double ...
DNA Topoisomerase II Beta (TOP2B) activity is essential for the expression of IEGs in a type of learning experience in mice ... June 2019). "Release of paused RNA polymerase II at specific loci favors DNA double-strand-break formation and promotes cancer ... While DNA methylation is necessary to inhibit genes involved in memory suppression, DNA demethylation is important in ... This causes the 5mC to enter the DNA demethylation pathway (see Figure titled "Initiation of DNA demethylation at a CpG site ...
... a type II topoisomerase, and topoisomerase iv, which is an enzyme necessary to separate replicated DNA, thereby inhibiting cell ... Drlica K, Zhao X (September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiology and Molecular Biology ... The usual adult dosage for the treatment of urinary tract infections is 1 gram daily, administered orally in two or four ... Urinary tract infections only 250 mg, capsules (prescription only) Cinoxacin mode of action involves the inhibiting of DNA ...
... there are two types of topoisomerases: type I produces transient single-strand breaks in DNA and types II produces transient ... and bacterial topo IV belong to the type II. We often forget that DNA gyrase does in fact have topoisomerase type II activity; ... As a result, the type I enzyme removes supercoils from DNA one at a time, whereas the type II enzyme removes supercoils two at ... also having topoisomerase II activity) we expect similarity in the two proteins' functions. DNA gyrase preliminary role is to ...
"Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism". Biochemical Society ... DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although only B-DNA and Z-DNA have been ... The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine ... Polymerases are classified according to the type of template that they use. In DNA replication, DNA-dependent DNA polymerases ...
... performs its function via a type IB topoisomerase mechanism causing the recombination of two separate strands of DNA. ... This pentad is made up of a lysine (Lysβ), two arginines (Arg I and II), a histidine (His-II), and a histidine/tryptophan (His/ ... If two different FRT sites are present within a cell, and FLP is present in appropriate concentrations, the FRT cassette will ... 2015) had a two-fold objective: characterize and compare the efficacy of Flp recombinase "knock-out" to Cre recombinase "knock- ...
The main two types are large, smooth, with a flat edge and elevated center and small, rough, and convex. A third type, mucoid, ... which protects DNA gyrase and topoisomerase IV from the effects of quinolone (fluoroquinolone) antibiotics such as ... methylation of 16S rRNA to prevent aminoglycoside binding and modification of DNA, or topoisomerase to protect it from the ... aeruginosa biofilm's matrix is composed of two types of sugars (or "exopolysacharides") named PSL and PEL: Polysaccharide ...
... is a type II topoisomerase inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer ... "On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs". Nucleic Acids Research. 41 ... Mitoxantrone is used to treat certain types of cancer, mostly acute myeloid leukemia. It improves the survival rate of children ... with double-stranded DNA". Biochemical Pharmacology. 34 (24): 4203-4213. doi:10.1016/0006-2952(85)90275-8. PMID 4074383. " ...
This issue is handled by decatenation of the two DNA molecules by a type II topoisomerase. Type II topoisomerases are also used ... For DNA polymerases to function, the double-stranded DNA helix has to be unwound to expose two single-stranded DNA templates ... During DNA replication, the replisome will unwind the parental duplex DNA into a two single-stranded DNA template replication ... Two replicative polymerases synthesize DNA in opposite orientations. Polymerase ε synthesizes DNA on the "leading" DNA strand ...
DNA polymerase and the DNA-dependent DNA polymerase type-B family (POLBc) conserved domain, which is linked with DNA binding, ... It also contains motif cores for DNA binding sites, catalytic residues, the active sites, and topoisomerase. The best ... Of the 113 ORFs that are likely to encode proteins, 66 are on the forward strand of DNA, the other 47 on the reverse. All of ... This region of HsNV-2's genome has similarity to the INT_REC_C conserved domain. This domain is related to phage integrase and ...
... stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA ... Daunorubicin is more abundantly found as a natural product because it is produced by a number of different wild type strains of ... This inhibits the progression of topoisomerase II, an enzyme which relaxes supercoils in DNA for transcription. ... The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered ...
"The interaction between p53 and DNA topoisomerase I is regulated differently in cells with wild-type and mutant p53". ... Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S (June 1994). "Two cellular proteins that bind to wild-type but not mutant ... "DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D". Genes & Development. 12 ( ... Hansson LO, Friedler A, Freund S, Rudiger S, Fersht AR (August 2002). "Two sequence motifs from HIF-1alpha bind to the DNA- ...
Crystal structure of the C-terminal domain of DNA topoisomerase IV ... Bacteria possess two closely related yet functionally distinct essential type IIA topoisomerases (Topos). DNA gyrase supports ... Structure of the topoisomerase IV C-terminal domain: a broken beta-propeller implies a role as geometry facilitator in ... Crystal structure of the C-terminal domain of DNA topoisomerase IV. *PDB DOI: https://doi.org/10.2210/pdb1WP5/pdb ...
Watt PM, Hickson ID (November 1994). "Structure and function of type II DNA topoisomerases". The Biochemical Journal. 303 (Pt 3 ... DNA topoisomerase IIα is a human enzyme encoded by the TOP2A gene. Topoisomerase IIα relieves topological DNA stress during ... Topoisomerase II TOP2B - Topoisomerase II beta Gene duplication Ataxia-telangiectasia TOPBP1 GRCh38: Ensembl release 89: ... "Entrez Gene: TOP2A topoisomerase (DNA) II alpha 170kDa". Emanuelli A, Borroni AP, Apel-Sarid L, Shah PA, Ayyathan DM, Koganti P ...
DNA Topoisomerases. EcoSal Plus. 2015:6 3. Watt PM, Hickson ID. Structure and function of type II DNA topoisomerases. The ... DNA topoisomerases can be classified as type I and type II enzymes [3, 6]. TOP2A is one of the isoenzymes which can mediate the ... catalytic activity of type II topoisomerases [6].. TOP2A (DNA topoisomerase II alpha) gene, mapped to chromosome 17q12-q21, ... 5. Bakshi RP, Galande S, Muniyappa K. Functional and regulatory characteristics of eukaryotic type II DNA topoisomerase. ...
Consequences for type II topoisomerase function",. abstract = "Type II topoisomerases resolve problematic DNA topologies such ... Electrostatics of DNA-DNA juxtapositions: Consequences for type II topoisomerase function. Journal of Physics Condensed Matter ... Electrostatics of DNA-DNA juxtapositions: Consequences for type II topoisomerase function. Graham L. Randall, B. Montgomery ... Electrostatics of DNA-DNA juxtapositions: Consequences for type II topoisomerase function. / Randall, Graham L.; Pettitt, B. ...
... the behavior of four nuclear matrix proteins during the various stages of apoptosis in the HL-60 cell line exposed to the DNA ... topoisomerase I inhibitor, camptothecin. We have examined the following antigens by immunocytochemical techniques: (i) the 180- ... DNA Topoisomerases, Type II / immunology * DNA Topoisomerases, Type II / metabolism * Fluorescent Antibody Technique, Indirect ... the 180-kDa nucleolar isoform of DNA topoisomerase II; (ii) a 126-kDa polypeptide of nuclear bodies; (iii) a 125-kDa protein; ...
Unfortunately, most drugs that target DNA topoisomerase II do not accumulate in wild type yeast cells to high enough. levels to ... We have found that vectors that overexpress topoisomerase II, or vectors that express a topoisomerase II mutant that is ... Novel DNA repair pathways required for cell survival following exposure to topoisomerase II targeting agents. Meiqin Liu; ... We are using this deletion set to identify all yeast genes that confer sensitivity to drugs targeting DNA topoisomerase II. ...
It has been proposed that both type IA and type II enzymes change conformation dramatically during the reaction cycle in order ... In order to change the topology of DNA, topoisomerases pass one or two DNA strands through transient single or double strand ... In order to change the topology of DNA, topoisomerases pass one or two DNA strands through transient single or double strand ... DNA topoisomerases are the enzymes responsible for maintaining the topological states of DNA. ...
IPR013824 DNA topoisomerase, type IA, central region, subdomain 1. IPR013825 DNA topoisomerase, type IA, central region, ... Cloning of cDNA encoding a novel mouse DNA topoisomerase III (Topo IIIbeta) possessing negatively supercoiled DNA relaxing ... IPR023405 DNA topoisomerase, type IA, core domain. IPR003602 DNA topoisomerase, type IA, DNA-binding domain ... IPR013826 DNA topoisomerase, type IA, central region, subdomain 3. ...
Our group has identified DNA topoisomerase IIα (Topo IIα) as one of the important mitotic proteins for SUMOylation. SUMOylated ... Mitotic SUMOylation: Unraveling the role of DNA Topoisomerase IIα SUMOylation and PIASy SUMO E3 ligase in mitosis. ... We have determined that Topo IIα CTD SUMOylation behaves like a signal transducer to induce a mitotic delay when Topo IIα is ... Further, we have shown that disruption of Topo II strand passage reaction (SPR) results in increased Topo IIα SUMOylation and ...
Topoisomerases are divided into two main types. Type I Topoisomerases act on one strand of double-stranded DNA, and they are ... Type II topoisomerases, on the other hand, are ATP-dependent and act on supercoiled DNA where the DNA is tangled around itself ... Type II topoisomerases are ATP-dependent enzymes that cut both strands of a DNA double helix. They are divided into two ... Type II topoisomerase reseals the broken ends of the DNA strands and finally detaches from the DNA- leaving behind an untangled ...
PDB Description: Topoisomerase VI-B, ADP-bound dimer form. PDB Compounds: (A:) Type II DNA topoisomerase VI subunit B. SCOPe ... Protein Topoisomerase VI-B subunit [82577] (1 species). contains an H2TH domain inserted in front of this domain and after the ... d1z5aa2 d.14.1.3 (A:307-469) Topoisomerase VI-B subunit {Sulfolobus shibatae [TaxId: 2286]} ... Family d.14.1.3: DNA gyrase/MutL, second domain [54224] (6 proteins). ...
The involvement of viral DNA-binding proteins in the regulation of virulence genes, transcription, DNA replication, and repair ... pA104R is a highly conserved HU/IHF-like DNA-packaging protein identified in the ASFV nucleoid that appears to be profoundly ... and a type II topoisomerase (P1192R), as well as the distinctive HU/IHF-like prokaryotic DNA-packaging protein (A104R). ... 3. The DNA Binding Protein pA104R 3.1. Structure of pA104R. ASFV ORF A104R (5-AR) predicts a type II DNA-binding protein of 104 ...
Coumermycin A1 efficacy was determined by the transcription of DNA gyrase, a type II DNA topoisomerase using reverse ... Objectives: Enrofloxacin, a fluoroquinolone antibiotic, is an inhibitor of prokaryotic topoisomerase II with antibacterial and ... Two separate groups (5 rabbits/each) treated topically (poured on at the base of the neck) with fipronil 5%, 1 vial/ 10 ... The two ruminant parasites, Paramphistomum cervi and Carmyerius gregarius, were collected from fresh-slaughtered native cattle ...
... these two domains are also found in the type II topoisomerase (DNA gyrase A) and in the alpha subunit of topoisomerase IV. ... from e.10.1.1 DNA topoisomerase I, 67K N-terminal domain: *Species Escherichia coli [TaxId:562] from e.10.1.1 DNA topoisomerase ... Fold e.10: Prokaryotic type I DNA topoisomerase [56711] (1 superfamily). 4 domains: (1) Toprim alpha/beta; (2&4) "winged helix ... Superfamily e.10.1: Prokaryotic type I DNA topoisomerase [56712] (2 families) duplication: the protein chain passing through ...
DNA binding - DNA replication - DNA topoisomerase (ATP-hydrolyzing) activity - DNA topoisomerase type I activity - DNA ... that OTIs can be used to direct the sites of etoposide-induced DNA cleavage mediated by topoisomerase IIα and topoisomerase IIβ ... DNA topoisomerases, especially type IIA topoisomerases, are proved therapeutic targets of anticancer and antibacterial drugs. ... Topoisomerase IIα expression correlated with cavernous sinus invasion.. CONCLUSIONS: The topoisomerase IIα expression ...
Which are released by DNA gyrases and topoisomerases *15. Termination  Two types rho dependent and rho independent.  ... Enzyme involved  DNA dependent RNA polymerase. The enzyme attaches itself at a specific on the DNA, the promoter site on the ... RNA editing  Central dogma is DNA  RNA  Protein. So change in DNA will be reflected into RNA and into protein, but sometimes ... Synthesis of RNA from DNA template  The primary transcript  DNA dependent RNA polymerase  Steps of RNA synthesis  RNA ...
... patients received epirubicin at clinically relevant doses after dose-escalation.Results of the topoisomerase activity will be ... regimen in patients with upper gastrointestinalmalignancies and breast cancer will be investigated as partof phase II studies, ... administered IV at a fixeddose of 250 mg/m2 on day 1 in combination with capecitabine at a fixeddose of 1,500 mg/m2 for days 2 ... Eukaryotic DNA topoisomerases: Two forms of type I DNA topoisomerases from HeLa cell nuclei. Proc Natl Acad Sci USA 78:3487- ...
... topoisomerases I, III and V) break single-strand DNA, and type II enzymes ( EC ; topoisomerases II, IV and VI) break ... DNA Topoisomerase I (eukaryota), DNA topoisomerase V, Vaccina virus topoisomerase, Variola virus topoisomerase, Shope fibroma ... The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and ... Human DNA Topoisomerase I (70 Kda) In Complex With The Indenoisoquinoline MJ-II-38 and Covalent Complex With A 22 Base Pair DNA ...
DNA Topoisomerase VI: a type II DNA topoisomerase present in Archaea and Eukarya. Poster by Cyril Buhler , Joyce H.G. Lebbink ... An atypical type II DNA topoisomerase from Archaea with implication for meiotic recombination. Nature (386, 414-417, 1997). A ... The Eighth Conference on DNA Topoisomerases in Therapy . Intrinsic ATPase Activity of the B Subunit of DNA Topoisomerase VI ... October 21-24 , 1996, New York City:The Seventh Conference On Dna Topoisomerases In Therapy. Posters by A. Bergerat and D. ...
Type II DNA Topoisomerase 13% * Thin Layer Chromatography 12% * Protein Subunits 11% ... 深入研究「Identification of the breakage-reunion subunit of T4 DNA topoisomerase」主題。共同形成了獨特的指紋。 ...
N2 - Type-II DNA topoisomerases resolve DNA entanglements such as supercoils, knots and catenanes by passing one segment of DNA ... AB - Type-II DNA topoisomerases resolve DNA entanglements such as supercoils, knots and catenanes by passing one segment of DNA ... Type-II DNA topoisomerases resolve DNA entanglements such as supercoils, knots and catenanes by passing one segment of DNA ... "Type-II DNA topoisomerases resolve DNA entanglements such as supercoils, knots and catenanes by passing one segment of DNA ...
... both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.. ... Fluoroquinolone resistance can arise through mutations in defined regions of DNA gyrase or topoisomerase IV, termed the ... Levofloxacin tablets should be administered at least two hours before or two hours after antacids containing magnesium, ... These agents should be taken at least two hours before or two hours after oral levofloxacin administration. ...
DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription ... The tablets contain a combination of two types of ciprofloxacin drug substance, ciprofloxacin hydrochloride and ciprofloxacin ... The bactericidal action of ciprofloxacin results from inhibition of topoisomerase II ( ... Rat Hepatocyte DNA Repair Assay (Positive) Thus, 2 of the 8 tests were positive, but results of the following 3 in vivo test ...
Brown PO, Cozzarelli NR "Catenation and knotting of duplex DNA by type 1 topoisomerases: a mechanistic parallel with type 2 ... of two viral DNA ends in a bimolecular disintegration reaction mediated by multimers of human immunodeficiency virus type 1 or ... Tsuchihashi Z, Brown PO "DNA strand exchange and selective DNA annealing promoted by the human immunodeficiency virus type 1 ... Brown PO, Peebles CL, Cozzarelli NR "A topoisomerase from Escherichia coli related to DNA gyrase." Proc Natl Acad Sci U S A ...
Human DNA topoisomerase II and bacterial DNA topoisomerase IV decatenation assays. Request a detailed protocol These ... Ng were tested on a gonococcal typing (GC) agar base with 1% defined growth supplement and Nm were tested on Mueller-Hinton ... Decatenation assays using purified human DNA topoisomerase II (ProFoldin, Hudson, MA), Ec DNA topoisomerase IV (ProFoldin, ... PTC-847 targets DNA synthesis, but not DNA topoisomerases. Our previous studies (Gerasyuto et al., 2018) established that a ...
These antibiotics act on the type II topoisomerases, type IV topoisomerases and DNA gyrase, which inhibits their function and ... The DNA topoisomerase is essential for normal physiological functions of the bacteria like DNA replication, recombination and ... The DNA gyrase and topoisomerase IV create a break in the bacterial chromosome, which leads to the fragmentation of the ... The DNA strands break, and this break will reduce the cells ability to repair the damaged DNA, which leads to cell death. ...
... did not induce significant DNA/topoisomerase I complex formation and did not inhibit RNA synthesis. Neither short-term nor long ... Transfer of a mutant p53 gene enhanced topotecan sensitivity in wild-type p53 LN-229 but not mutant p53 LN-18 cells. CD95 ... Topotecan is a novel topoisomerase I inhibitor that may have a role in the adjuvant chemotherapy of several solid tumors, ... induced DNA fragmentation, did not induce major cell cycle changes, failed to consistently alter BCL-2 or BAX protein levels ...
"DNA supercoiling inhibits DNA knotting". April 15, 2008, "Type II Topoisomerase Models". October 23, 2007, "Resolution of DNA ... "DNA Unknotting by Human Topoisomerase IIα". *International Summer School on "DNA and Chromosomes: Physical and Biological ... "Unknotting by Type II Topoisomerases". *Celebration of the Career of Clay C. Ross, The University of the South, Sewanee, TN, ... "Topology of Type II Topoisomerases". *"Mathematics and Molecular Biology VII: Modeling Across the Scales- Atoms to Organisms," ...
Two type I topoisomerases maintain DNA topology in human mitochondria. Title: Two type I topoisomerases maintain DNA topology ... domain found in members of the type IA family of DNA topoisomerases (Topo IA) similar to topoisomerase III. Type IA DNA ... DNA topoisomerase 3-alpha. Names. topo III-alpha. topoisomerase (DNA) III alpha. zinc finger, GRF-type containing 7. NP_ ... TOP1Ac; DNA Topoisomerase, subtype IA; DNA-binding, ATP-binding and catalytic domain of bacterial DNA topoisomerases I and III ...
  • We found that several genes also confer high levels of sensitivity to mAMSA including strains with mutations in HPR5, a helicase involved in funneling DNA lesion into recombination-repair pathways, ASF1, a chromatin assembly factor that is required for gene silencing, and CTF4, a DNA polymerase alpha binding protein important for genome stability. (aacrjournals.org)
  • In this study we focused our attention on the behavior of four nuclear matrix proteins during the various stages of apoptosis in the HL-60 cell line exposed to the DNA topoisomerase I inhibitor, camptothecin. (nih.gov)
  • 3,5] The additive/synergistic effect of sequential topoisomerase I and II inhibitor administration has been examined in vivo in several phase I and II human trials that explored their sequential administration. (cancernetwork.com)
  • These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG. (psu.edu)
  • Etoposide (Vepesid, VP-16), an inhibitor of topoisomerase II, is a chemotherapeutic drug commonly used for treatment of different types of malignant diseases. (nel.edu)
  • SN-38, a topoisomerase I inhibitor (chemotherapy), which damages the tumor cell's DNA and inhibits further DNA replication. (everyone.org)
  • Here we report the crystal structure of the C-terminal domain of Topo IV ParC subunit (ParC-CTD) from Bacillus stearothermophilus and provide a structure-based explanation for how Topo IV and DNA gyrase execute distinct activities. (rcsb.org)
  • Although the topological connectivity of ParC-CTD is similar to the recently determined CTD structure of DNA gyrase GyrA subunit (GyrA-CTD), ParC-CTD surprisingly folds as a previously unseen broken form of a six-bladed beta-propeller. (rcsb.org)
  • Interestingly, all three mutants also showed only modest effects on sensitivity to the topoisomerase I targeting agent camptothecin. (aacrjournals.org)
  • Our results may also provide important clues to the differences in cellular responses to drugs targeting such as camptothecin, that target topoisomerase I and drugs such as etoposide that target topoisomerase II. (aacrjournals.org)
  • In addition to its role in these fundamental processes, the biological importance of eukaryotic DNA topoisomerase I is underscored by its identification as the target of the antitumor alkaloid camptothecin. (northwestern.edu)
  • Conclusion Crystallographic, biochemical and genetic data indicate that this 26 kDa fragment of yeast DNA topoisomerase I is involved in complex formation between the enzyme and DNA, and probably also in camptothecin-enzyme-DNA ternary complex formation. (northwestern.edu)
  • Prior exposure of KB cells to 42°C enhanced the cytotoxicity of VP-16, but not that of a topoisomerase I-targeting agent, a camptothecin analogue, CPT-11. (elsevierpure.com)
  • abstract = "The recent discovery of DNA sequences responsible for the specific attachment of chromosomal DNA to the nuclear skeleton (MARs/SARs) was an important step towards our understanding of the functional and structural organization of eukaryotic chromatin [Mirkovitch et al. (nebraska.edu)
  • Because of the structure of duplex DNA, it inevitably leads the consequences of the topology such as supercoils [ 2 ]. (jcancer.org)
  • DNA topoisomerases, ubiquitously present in eukaryotes, archaebacteria and Eubacteria, are necessary for the regulation of DNA topology in various cellular procedures [ 3 , 4 ]. (jcancer.org)
  • This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus altering the topology of DNA. (cancerindex.org)
  • T opoisomerase enzymes I and II play a critical role in preserving DNA topology by producing transient single- and double-strand DNA breaks that relieve supercoiling during replication, recombination, chromosomal decondensation, and RNA transcription. (cancernetwork.com)
  • Human type II topoisomerases (TopoII) are essential for controlling DNA topology within the cell. (h-its.org)
  • Propeller breakage is due to the absence of a DNA gyrase-specific GyrA box motif, resulting in the reduction of curvature of the proposed DNA binding region, which explains why ParC-CTD is less efficient than GyrA-CTD in mediating DNA bending, a difference that leads to divergent activities of the two homologous enzymes. (rcsb.org)
  • According to their different acting mechanisms, DNA topoisomerases can be classified as type I and type II enzymes [ 3 , 6 ]. (jcancer.org)
  • DNA topoisomerases are the enzymes responsible for maintaining the topological states of DNA. (rcsb.org)
  • It has been proposed that both type IA and type II enzymes change conformation dramatically during the reaction cycle in order to accomplish these transformations. (rcsb.org)
  • eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. (embl.de)
  • Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. (embl.de)
  • This entry represents the C-terminal region of DNA topoisomerase I enzymes from eukaryotes (type IB enzymes). (embl.de)
  • Background: Type I DNA topoisomerases, divided mechanistically into two subfamilies, are ubiquitous enzymes that participate in replication and transcription. (northwestern.edu)
  • It inhibits bacterial topoisomerase IV and DNA gyrase (topoisomerases type II), enzymes required for DNA replication, transcription, repair, and recombination. (medscape.com)
  • The targets of quinolone activity are the bacterial DNA gyrase and topoisomerase IV, enzymes essential for DNA replication and transcription. (cdc.gov)
  • Quinolones inhibit two enzymes that are required for bacterial DNA synthesis, i.e. (cdc.gov)
  • DNA gyrase and topoisomerase IV to plasmids that have been included in also included in the study. (cdc.gov)
  • DNA gyrase and topoisomerase IV. (cdc.gov)
  • Thus, when topoisomerase I inhibition occurs with agents such as SN-38 in cell lines, the cells compensate by increasing expression of topoisomerase II and vice versa. (cancernetwork.com)
  • 3] This antagonism might be related to topoisomerase I inhibition of DNA synthesis, which is required for the cytotoxic effect of topoisomerase II-induced cleavable complexes. (cancernetwork.com)
  • prevent quinolone inhibition ( 2 , 3 ). (cdc.gov)
  • Moxifloxacin is a fluoroquinolone antibiotic that inhibits A subunits of DNA gyrase (topoisomerase type II) and topoisomerase IV, resulting in inhibition of bacterial DNA replication and transcription. (medscape.com)
  • Intrastrand cross-linking of DNA and inhibition of DNA precursors are among the proposed mechanisms of action for cisplatin. (medscape.com)
  • DNA gyrase supports replication and transcription with its unique supercoiling activity, whereas Topo IV preferentially relaxes (+) supercoils and is a decatenating enzyme required for chromosome segregation. (rcsb.org)
  • Topoisomerase IIα relieves topological DNA stress during transcription, condenses chromosomes, and separates chromatids. (wikipedia.org)
  • TOP2A encodes an enzyme which is implicated in almost any process of DNA metabolism including transcription, replication, movement and untangling [ 3 , 8 , 9 ], which catalyze the passage of two DNA duplexes across each other to resolve the entanglements and coiling of cellular DNA [ 10 ]. (jcancer.org)
  • The involvement of viral DNA-binding proteins in the regulation of virulence genes, transcription, DNA replication, and repair make them significant targets. (mdpi.com)
  • This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. (cancerindex.org)
  • Stabilization of covalent complexes, converting topoisomerases into DNA damage, is an essential aspect of cell killing by these drugs. (aacrjournals.org)
  • The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that 'clamps' around essentially B-form DNA. (embl.de)
  • The formation of cleavable DNA-topoisomerase II-VP-16 complexes was also greatly increased by prior exposure to 42°C. Our present study proposes the hypothesis that the topoisomerase II gene might be one of the heat-shock-inducible genes and that hyperthermic anticancer therapy with topoisomerase II-targeting antitumor agents can be improved. (elsevierpure.com)
  • It has been shown that topoisomerase II and histone H1 were capable of a specific interaction with SARs by the formation of precipitable complexes [Adachi et al. (nebraska.edu)
  • We recently reported that enzyme-mediated DNA cleavage complexes (in which TopoII is covalently linked to the cleaved DNA during catalysis) formed in the presence of the anticancer drug etoposide persisted approximately 3-fold longer with TopoIIα than TopoIIβ. (h-its.org)
  • We also used smoothed potential MD to estimate etoposide dissociation kinetics from the two isoform complexes. (h-its.org)
  • Both diseases involve the BRAFT and FANCM complexes, which are important in DNA repair. (medscape.com)
  • It modulates the topological states of DNA by transient cleavage, strand passing and religation of double-stranded DNA resulting in decatenation of intertwined DNA molecules and relaxation of supercoiled DNA [ 8 , 9 ]. (jcancer.org)
  • The time course and characteristics of the genomic breakpoints in the present t-AML cases support the hypothesis of translocation formation as a result of defective breakage repair after topoisomerase II cleavage. (uni-luebeck.de)
  • For this reason, there are a number of TopoII-targeted anticancer drugs that act by inducing DNA cleavage mediated by both TopoII isoforms (TopoIIα and TopoIIβ) in cells. (h-its.org)
  • Occupational exposure limits with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. (cdc.gov)
  • Type II topoisomerases resolve problematic DNA topologies such as knots, catenanes, and supercoils that arise as a consequence of DNA replication and recombination. (utmb.edu)
  • Type-II DNA topoisomerases resolve DNA entanglements such as supercoils, knots and catenanes by passing one segment of DNA duplex through a transient enzyme-bridged double-stranded break in another segment. (elsevierpure.com)
  • DNA topoisomerase IIα is a human enzyme encoded by the TOP2A gene. (wikipedia.org)
  • Two forms of this enzyme exist as likely products of a gene duplication event. (wikipedia.org)
  • TOP2A (DNA topoisomerase II alpha) gene, mapped to chromosome 17q12-q21, covers approximately 27.5 kb and includes 35 exons, encoding a 170 kDa protein [ 7 ]. (jcancer.org)
  • Sääf AM, Halbleib JM, Chen X, Tsan Yuen S, Yi Leung S, Nelson WJ, Brown PO "Parallels between Global Transcriptional Programs of Polarizing Caco-2 Intestinal Epithelial Cells In Vitro and Gene Expression Programs in Normal and Colon Cancer. (openwetware.org)
  • Palmer C, Diehn M, Alizadeh AA, Brown PO "Cell-type specific gene expression profiles of leukocytes in human peripheral blood. (openwetware.org)
  • [ 7 , 8 ] Sister chromatid exchanges are considered a sensitive indicator for cell genome instability, as they are thought to be the outcome of DNA double-strand breaks resulting from homologous recombination repair. (medscape.com)
  • It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another. (wikipedia.org)
  • A number of studies have indicated that DNA topoisomerases play an essential role in the DNA world through allowing DNA double helices or strands to cut across each other [ 4 , 5 ]. (jcancer.org)
  • Type II DNA topoisomerase breaks both DNA strands, and many anticancer agents including etoposide (VP-16) and teniposide (VM-26) have been developed by targeting topoisomerase II molecules. (elsevierpure.com)
  • Smoothed Potential MD Simulations for Dissociation Kinetics of Etoposide To Unravel Isoform Specificity in Targeting Human Topoisomerase II. (h-its.org)
  • In this study, we report the results of classical molecular dynamics (MD) simulations to comparatively analyze the molecular interactions formed within the TopoII/DNA/etoposide complex with both isoforms. (h-its.org)
  • These extensive classical and enhanced sampling simulations revealed stabilizing interactions of etoposide with two serine residues (Ser763 and Ser800) in TopoIIα. (h-its.org)
  • The bipartite DNA-binding regions of the 26 kDa fragment may enable eukaryotic DNA topoisomerase I to adapt to sequence-dependent structural variations in its DNA substrates. (northwestern.edu)
  • TOP2A is one of the isoenzymes which can mediate the catalytic activity of type II topoisomerases [ 6 ]. (jcancer.org)
  • While the antibody to the nucleolar isoform of DNA topoisomerase II gave a fluorescent pattern that was well-maintained until the late phases of apoptosis, the other three nuclear antigens showed marked modifications in their distribution. (nih.gov)
  • It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
  • There appeared 5-fold or higher increases in mRNA levels of both topoisomerase II and a heat shock protein, hsp-70, after exposure to 42°C for 3 h, but only a slight, if any, increase in topoisomerase I mRNA. (elsevierpure.com)
  • Topotecan inhibits topoisomerase I, inhibiting DNA replication. (medscape.com)
  • DNA topoisomerase, Toprim domain [Interproscan]. (ntu.edu.sg)
  • Hin-Mediated DNA Knotting and Recombination Promote Replicon Dysfunction and Mutation , Richard W. Deibler * , Jennifer K. Mann * , De Witt L. Sumners and E. Lynn Zechiedrich. (utexas.edu)
  • This protein plays a pivotal role in DNA recombination and repair. (medscape.com)
  • 14(2): 1-5, 2023. (bvsalud.org)
  • Case-patients 1 and 2 (sisters) left Johannesburg on January 15, 2023, and traveled together to Chinsapo, Lilongwe, Malawi, in one of the districts reporting active outbreaks, where they stayed until their departure on January 29, 2023. (cdc.gov)
  • The interesting activities of a subset of 4-hydoxy-2-pyridones provided the impetus for synthesis of additional chemotypes with this core ( Figure 1 ) and their evaluation for effectiveness against additional pathogenic strains including Ng and N. meningitidis (Nm ). (elifesciences.org)
  • They inhibit DNA synthesis through the formation of DNA cross-links. (medscape.com)
  • Ifosfamide forms DNA interstrand and intrastrand bonds that interfere with protein synthesis. (medscape.com)
  • They interfere with DNA synthesis by blocking the methylation of deoxyuridylic acid. (medscape.com)
  • Despite their biological and clinical importance, little is understood about how a topoisomerase differentiates DNA topologies in a molecule that is significantly larger than the topoisomerase itself. (utmb.edu)
  • The process by which a DNA molecule is duplicated. (bvsalud.org)
  • Such catastrophic consequences make topoisomerases an effective target for antibiotics and anticancer agents. (utmb.edu)
  • Here we directly observed the strand passage by human topoisomerase IIα, after winding a pair of fluorescently stained DNA molecules with optical tweezers for 30 turns into an X-shaped braid. (elsevierpure.com)
  • The authors present two small molecules that specifically target the essential ribonucleotide reductase of the causative agent of gonorrhea. (elifesciences.org)
  • Agents targeting DNA topoisomerases are active against a wide range of human tumors. (aacrjournals.org)
  • They work by binding to topoisomerase and causing single-strand DNA breaks. (medscape.com)
  • We have found that vectors that overexpress topoisomerase II, or vectors that express a topoisomerase II mutant that is hypersensitive to DNA intercalating agents confers a high enough level of sensitivity to mAMSA to allow efficient screening of the yeast deletion strains. (aacrjournals.org)
  • Topoisomerase-inhibiting antineoplastic agents prevent cell growth and proliferation. (medscape.com)
  • Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe [ 1 ], and it is expected to overtake lung carcinoma as the second leading cause by 2030 [ 2 ]. (hindawi.com)
  • The most frequent type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which accounts for up to 90% of pancreatic adenocarcinoma cases [ 3 ]. (hindawi.com)
  • 3] This is believed to constitute an important mechanism of resistance to topoisomerase I inhibitors in malignant cells. (cancernetwork.com)
  • Among them, the Provi- plasmid-mediated, and thus transfer- bacterial isolates, our objective was to dencia stuartii and Proteus mirabilis able, quinolone resistance determi- use replicon typing to trace a possible isolates from Algeria were negative nants has been recently discovered ( 1 ) dissemination of a common plasmid for qnrA1 . (cdc.gov)
  • Amplicons were confi rmed by DNA qnrA1 genes may be identifi ed on a means that 1 plasmid scaffold has sequencing and used as probes in hy- single genetic structure in several iso- brought the same (or at least very sim- bridization experiments on purifi ed lates has been recently shown with ilar) multidrug resistance to multiple plasmids (data not shown). (cdc.gov)
  • Based on reported resistance of Ng strains, the CDC currently prescribes a two antibiotic protocol using ceftriaxone (a β-lactam) and azithromycin (a macrolide). (elifesciences.org)
  • It has been proposed that type II topoisomerases recognize angle and curvature between two DNA helices characteristic of knotted and catenated DNA to account for the enzyme's preference to unlink instead of link DNA. (utmb.edu)
  • In Drosophila Hadlaczky et al 1988 found DNA topoisomerase II α to correlate with cell proliferation - but β did not. (wikipedia.org)
  • The possible role of ParC-CTD as a geometry facilitator during various catalytic events and the evolutionary relationships between prokaryotic type IIA Topos have also been discussed according to these new structural insights. (rcsb.org)
  • The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. (embl.de)
  • Results The three-dimensional structure of a 26 kDa fragment (residues 135 to about 363) of Saccharomyces cerevisiae DNA topoisomerase I has been determined at 1.9 å resolution. (northwestern.edu)
  • We have taken advantage of newly developed yeast genomic tools to identify genes encoding DNA repair or DNA damage tolerance functions that play key roles in sensitivity to drugs targeting topoisomerases. (aacrjournals.org)
  • Deletions of all genes that are not essential for viability have been screened for a wide range of phenotypes, including sensitivity to a variety of different DNA damaging agents. (aacrjournals.org)
  • We are using this deletion set to identify all yeast genes that confer sensitivity to drugs targeting DNA topoisomerase II. (aacrjournals.org)
  • cMonkey tries to identify two motifs per modules in the upstream sequences of the module member genes. (systemsbiology.net)
  • By evaluating the tumor microenvironment, we observed that the immune and metabolic microenvironments of the two groups were substantially different. (hindawi.com)
  • Lymphokine-activated killer (LAK) cells are produced from the patient's T cells which are extracted from the tumor and grown in a cell culture system with the lymphokine interleukin-2 (IL-2). (msdmanuals.com)
  • Antibodies targeting two tumor antigens and CD3 are being tested. (msdmanuals.com)
  • Here, we show several unique cases that can only be observed for remote epitaxy, distinguishable from other two-dimensional material-based epitaxy mechanisms. (bvsalud.org)