All Topics  
Topoisomerase

 

 
   Email Print
   Bookmark   Link
 

 

Topoisomerase
 
 
  Topics Topoisomerase Topic Home

Topoisomerases (type I: , type II: ) are isomerase
Isomerase

In biochemistry, an isomerase is an enzyme that catalyzes the structural rearrangement of isomers. Isomerases thus catalyze reactions of the form...
 enzymes that act on the topology
DNA topology

DNA topology is the focus of an interdiscipline between molecular biology and mathematics and as a term refers to DNA supercoiling, knotting and catenation....
 of DNA
DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
.

Function The double-helical
Double helix

In geometry a double helix typically consists of two congruence helix with the same axis, differing by a translation along the axis, which may or may not be half-way....
 configuration that DNA strands naturally reside in makes them difficult to separate, and yet they must be separated by helicase
Helicase

Helicases are a class of proteins vital to all living organisms. They are motor proteins that move directionally along a nucleic acid Phosphodiester bond, separating two Annealing nucleic acid strands using energy derived from nucleotide hydrolysis....
 proteins if other enzymes are to transcribe
Transcription (genetics)

Transcription is the synthesis of RNA under the direction of DNA. RNA synthesis, or transcription, is the process of transcribing DNA nucleotide sequence information into RNA sequence information....
 the sequences
DNA sequence

A DNA sequence or genetic sequence is a succession of letters representing the primary structure of a real or hypothetical DNA molecule or strand, with the capacity to carry information as described by the central dogma of molecular biology....
 that encode
Genetic code

The genetic code is the set of rules by which information encoded in genetic material is Translation into proteins by living cell s. The code defines a mapping between tri-nucleotide sequences, called codons, and amino acids....
 protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
s, or if chromosomes are to be replicated
DNA replication

DNA replication, the basis for heredity, is a fundamental process occurring in all living organisms to copy their DNA. This process is "semiconservative replication" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand....
.






Discussion
Ask a question about 'Topoisomerase'
Start a new discussion about 'Topoisomerase'
Answer questions from other users
Full Discussion Forum



Encyclopedia


Topoisomerases (type I: , type II: ) are isomerase
Isomerase

In biochemistry, an isomerase is an enzyme that catalyzes the structural rearrangement of isomers. Isomerases thus catalyze reactions of the form...
 enzymes that act on the topology
DNA topology

DNA topology is the focus of an interdiscipline between molecular biology and mathematics and as a term refers to DNA supercoiling, knotting and catenation....
 of DNA
DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
.

Discovery


Topoisomerases were first discovered by Harvard Professor James C. Wang
James C. Wang

James C. Wang is a Harvard University Professor of biochemistry and molecular biology. Wang was the first discoverer of topoisomerases. He was elected as an academician of the Taiwan Academia Sinica in 1982 and a member of the United States National Academy of Science in 1986....
.

Function

The double-helical
Double helix

In geometry a double helix typically consists of two congruence helix with the same axis, differing by a translation along the axis, which may or may not be half-way....
 configuration that DNA strands naturally reside in makes them difficult to separate, and yet they must be separated by helicase
Helicase

Helicases are a class of proteins vital to all living organisms. They are motor proteins that move directionally along a nucleic acid Phosphodiester bond, separating two Annealing nucleic acid strands using energy derived from nucleotide hydrolysis....
 proteins if other enzymes are to transcribe
Transcription (genetics)

Transcription is the synthesis of RNA under the direction of DNA. RNA synthesis, or transcription, is the process of transcribing DNA nucleotide sequence information into RNA sequence information....
 the sequences
DNA sequence

A DNA sequence or genetic sequence is a succession of letters representing the primary structure of a real or hypothetical DNA molecule or strand, with the capacity to carry information as described by the central dogma of molecular biology....
 that encode
Genetic code

The genetic code is the set of rules by which information encoded in genetic material is Translation into proteins by living cell s. The code defines a mapping between tri-nucleotide sequences, called codons, and amino acids....
 protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
s, or if chromosomes are to be replicated
DNA replication

DNA replication, the basis for heredity, is a fundamental process occurring in all living organisms to copy their DNA. This process is "semiconservative replication" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand....
. In so-called circular DNA
Circular DNA

Circular DNA is a form of DNA that is found in bacteria and archaea as well as in eukaryote cells in the form of mitochondrial DNA.While the individual strands of a linear double helix represent two distinct and separable molecules, this need not be true for circular DNA....
, in which double helical DNA is bent around and joined in a circle
Circle

A circle is a simple shape of Euclidean geometry consisting of those point in a plane which are the same distance from a given point called the center....
, the two strands are topologically linked, or knotted
Knot theory

In mathematics, knot theory is the area of topology that studies knot s. While inspired by knots which appear in daily life in shoelaces and rope, a mathematician's knot differs drastically in that the ends are joined together to prevent it from becoming undone....
. Otherwise identical loops of DNA having different numbers of twists are topoisomer
Topoisomer

Topoisomers or topological isomers are molecules with the same chemical formula and stereochemical bond connectivities but different topology....
s, and cannot be interconverted by any process that does not involve the breaking of DNA strands. Topoisomerases catalyze and guide the unknotting of DNA by creating transient breaks in the DNA using a conserved Tyrosine
Tyrosine

Tyrosine or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cell to protein biosynthesis proteins. This is a non-essential amino acid and it is found in casein....
 as the catalytic residue.

The insertion of viral DNA into chromosomes and other forms of recombination
Recombination

Recombination may refer to:* Genetic recombination, the process by which genetic material is broken and joined to other genetic material* Carrier generation and recombination, processes by which mobile electrons and electron holes are created and eliminated...
 can also require the action of topoisomerases.

Clinical significance

See also topoisomerase inhibitor
Topoisomerase inhibitor

Topoisomerase inhibitors are agents designed to interfere with the action of topoisomerase enzymes , which are enzymes that control the changes in DNA structure by enzyme catalysis the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle....
Many drugs operate through interference with the topoisomerases. The broad-spectrum fluoroquinolone
Quinolone

The quinolones are a family of chemical synthesis broad-spectrum antibiotics. The wikt:parent compound of the group is nalidixic acid. The majority of quinolones in clinical use belong to the subset of fluoroquinolones, which have a fluorine atom attached the central ring system, typically at the 6-position....
 antibiotic
Antibiotic

In common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria. Antibiotics belong to the group of antimicrobial compounds used to treat infections caused by microorganisms, including fungus and protozoa....
s act by disrupting the function of bacterial type II topoisomerases.

Some chemotherapy
Chemotherapy

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer....
 drugs work by interfering with topoisomerases in cancer
Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
 cells
Cell (biology)

The cell is the structural and functional unit of all known Life organisms. It is the smallest unit of an organism that is classified as living, and is often called the building bricks of life....
:
  • type 1 is inhibited by irinotecan
    Irinotecan

    Irinotecan is a chemotherapy agent that is a Type I topoisomerase Enzyme inhibitor. Chemically, it is a semisynthetic analogue of the natural alkaloid camptothecin....
     and topotecan
    Topotecan

    Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase Enzyme inhibitor. It is the water-soluble derivative of camptothecin. It is used to treat ovarian cancer and lung cancer, as well as other cancer types....
    .
  • type 2 is inhibited by etoposide
    Etoposide

    Etoposide phosphate is an inhibitor of the enzyme topoisomerase II. It is used as a form of chemotherapy for malignancies such as Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme....
    (VP-16), teniposide
    Teniposide

    Teniposide is a chemotherapy medication mainly used in the treatment of childhood acute lymphocytic leukemia. It is in a class of drugs known as podophyllotoxin derivatives and slows the growth of cancer cells in the body....
     and HU-331, a quinolone synthesized from cannabidiol
    Cannabidiol

    Cannabidiol, also known as CBD, is a Cannabinoids found in Cannabis. It is a major constituent of the plant, representing up to 40% in its extracts....
    .


Topoisomerase I is the antigen
Antigen

An antigen is a substance that prompts the generation of antibodies and can cause an immune response. The word originated from the notion that they can stimulate antibody generation....
 recognized by Anti Scl-70 antibodies in scleroderma
Scleroderma

Systemic scleroderma is a systemic connective tissue disease.It is also known as "systemic Sclerosis "....
.

Topological problems

There are three main types of topology: supercoiling
DNA supercoil

In a "relaxed" double-helical segment of DNA, the two strands twist around the helical axis once every 10.4-10.5 base pairs of DNA sequence. Adding or subtracting twists, as some enzymes can do, imposes strain....
, knotting and catenation
Catenation

Catenation is the ability of a chemical element to form a long chain-like structure via a series of covalent bonds. Catenation occurs most readily in carbon, which forms covalent bonds with other carbon atoms.Catenation is the reason for the presence of large number of organic compounds in nature....
. When outside of replication
DNA replication

DNA replication, the basis for heredity, is a fundamental process occurring in all living organisms to copy their DNA. This process is "semiconservative replication" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand....
 or transcription
Transcription (genetics)

Transcription is the synthesis of RNA under the direction of DNA. RNA synthesis, or transcription, is the process of transcribing DNA nucleotide sequence information into RNA sequence information....
, DNA needs to be kept as compact as possible and these three states help this cause. However when transcription or replication occur, DNA needs to be free and these states seriously hinder the processes. In addition, during replication, the newly replicated duplex of DNA and the original duplex of DNA become intertwined and need to be completely separated in order to ensure genomic integrity as a cell divides.

Classes


Topoisomerases can fix these topological problems and are separated into two types separated by the number of strands cut in one round of action:
  • Type I topoisomerase
    Type I topoisomerase

    Type I topoisomerases are divided into two structurally and mechanistically distinct topoisomerases: type IA and type IB.* Type IA topoisomerases change the linking number of a circular DNA strand by units of strictly 1....
     cuts one strand of a DNA double helix and then reanneals the cut strand. Type I topoisomerases are subdivided into two subclasses: type IA topoisomerases which share many structural and mechanistic features with the type II topoisomerases, and type IB topoisomerases, which utilize a controlled rotary mechanism. Examples of type IA topoisomerases include topo I and topo III. Historically, type IB topoisomerases were referred to as eukaryotic topo I, but IB topoisomerases are present in all three domains of life. Interestingly, type IA topoisomerases form a covalent intermediate with the 5' end of DNA, while the IB topoisomerases form a covalent intermediate with the 3' end of DNA. Recently, a type IC topoisomerase has been identified, called topo V. While it is structurally unique from type IA and IB topoisomerases, it shares a similar mechanism with type IB topoisomerase.


  • Type II topoisomerase
    Type II topoisomerase

    Type II topoisomerases cut both strands of the DNA helix simultaneously in order to change the linking number of the molecule....
     cuts both strands of one DNA double helix, passes another unbroken DNA strand through it, and then reanneals the cut strand. It is also split into two subclasses: type IIA and type IIB topoisomerases, which share similar structure and mechanisms. Examples of type IIA topoisomerases include eukaryotic topo II, E. coli gyrase, and E. coli topo IV. Examples of type IIB topoisomerase include topo VI.


Both type I and type II topoisomerases change the linking number
Linking number

In mathematics, the linking number is a numerical invariant that describes the linking of two closed curves in three-dimensional space. Intuitively, the linking number represents the number of times that each curve winds around the other....
 of DNA. Type IA topoisomerases change the linking number by one, type IB and type IC topoisomerases change the linking number by any integer, while type IIA and type IIB topoisomerases change the linking number by two.

See also


  • DNA topology
    DNA topology

    DNA topology is the focus of an interdiscipline between molecular biology and mathematics and as a term refers to DNA supercoiling, knotting and catenation....
  • Supercoil
  • TOP1
    TOP1

    Topoisomerase I, also known as TOP1, is a human gene....


External links