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Encyclopedia > Topoisomerase
Topoisomerase I solves the problem caused by tension generated by winding/unwinding of DNA. It wraps around DNA and makes a cut permitting the helix to spin. Once DNA is relaxed, topoisomerase reconnects broken strands (PDB 1a36)
Topoisomerase I solves the problem caused by tension generated by winding/unwinding of DNA. It wraps around DNA and makes a cut permitting the helix to spin. Once DNA is relaxed, topoisomerase reconnects broken strands (PDB 1a36)

Topoisomerase (type I: EC 5.99.1.2, type II: EC 5.99.1.3) is an isomerase enzyme that acts on the topology of DNA which was discovered by Harvard Professor James C. Wang.[1] Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... In biochemistry, an isomerase is any enzyme that catalyses the interconversion of isomers. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... DNA topology is the focus of a subdiscipline within molecular biology and as a term refers to both the knot-like arrangements that segments of DNA may assume and to the mathematics that pertains to them. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ...

Contents

Function

The double-helical configuration that DNA strands naturally reside in makes them difficult to separate, and yet they must be separated by helicase proteins if other enzymes are to transcribe the sequences that encode proteins, or if chromosomes are to be replicated. In so-called circular DNA, in which double helical DNA is bent around and joined in a circle, the two strands are topologically linked, or knotted. Otherwise identical loops of DNA having different numbers of twists are topoisomers, and cannot be interconverted by any process that does not involve the breaking of DNA strands. Topoisomerases catalyze and guide the unknotting of DNA. The Double-Helix are an alien race in the Wing Commander science fiction series. ... This article or section does not adequately cite its references or sources. ... A micrograph of ongoing gene transcription of ribosomal RNA illustrating the growing primary transcripts. ... part of a DNA sequence A DNA sequence (sometimes genetic sequence) is a succession of letters representing the primary structure of a real or hypothetical DNA molecule or strand, The possible letters are A, C, G, and T, representing the four nucleotide subunits of a DNA strand (adenine, cytosine, guanine... RNA codons. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... This article is about the biological chromosome. ... This article or section is in need of attention from an expert on the subject. ... While the individual strands of a linear double helix represent two distinct and separable molecules, this need not be true for circular DNA. If the strands twist an odd number of times around one another in completing the DNA loop, then they are covalently joined into a single molecule. ... Circle illustration This article is about the shape and mathematical concept of circle. ... Trefoil knot, the simplest non-trivial knot. ... Topoisomers or topological isomers are molecules with the same chemical formula but different topologies. ...


The insertion of viral DNA into chromosomes and other forms of recombination can also require the action of topoisomerases. Recombination usually refers to the biological process of genetic recombination and meiosis, a genetic event that occurs during the formation of sperm and egg cells. ...


Clinical significance

See also topoisomerase inhibitor

Many drugs opoopperate through interference with the topoisomerases. The broad-spectrum fluoroquinolone antibiotics act by disrupting the function of bacterial type II topoisomerases. Topoisomerase inhibitors are chemotherapy agents designed to interfere with the action of topoisomerase enzymes (topoisomerase I and II), which are enzymes that control the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. ... Quinolones and fluoroquinolones form a group of broad-spectrum antibiotics. ... Staphylococcus aureus - Antibiotics test plate. ...


Some chemotherapy drugs work by interfering with topoisomerases in cancer cells: Chemotherapy is the use of chemical substances to treat disease. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... Drawing of the structure of cork as it appeared under the microscope to Robert Hook from Micrographia which is the origin of the word cell. Cells in culture, stained for keratin (red) and DNA (green). ...

Irinotecan is a chemotherapy agent that is a topoisomerase 1 inhibitor. ... Topotecan (Hycamtin®) is a chemotherapy agent that is a topoisomerase 1 inhibitor. ... Etoposide: chemical structure Etoposide phosphate (Eposin®, Etopophos®, Vepesid®, VP-16®) is an inhibitor of the enzyme topoisomerase II. It is used as a form of chemotherapy for malignancies such as lung cancer, testicular cancer, lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme. ... Teniposide is a prescribed medication mainly used to treat childhood acute lymphocytic leukemia. ...

Topological problems

There are three main types of topology; supercoiling, knotting and catenation. When outside of replication or transcription 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 a relaxed double-helical segment of DNA, the two strands twist around the helical axis once every 10. ... The requested page title was invalid, empty, an incorrectly linked inter-language or inter-wiki title, or contained illegal characters. ... Catenation is the ability of a chemical element to form covalent bonds with itself, resulting in ring, chain and cage molecules. ... This article or section is in need of attention from an expert on the subject. ... A micrograph of ongoing gene transcription of ribosomal RNA illustrating the growing primary transcripts. ...


Types

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 cuts one strand, passes the other through it then reanneals the cut strand.
  • Type II topoisomerase cuts both strands, and passes an unbroken double strand through it then reanneals the cut strand.

Both type I and type II topoisomerases change the linking number of DNA. Topoisomerase I solves the problem caused by tension generated by winding/unwinding of DNA. It wraps around DNA and makes a cut permitting the helix to spin. ... Structure of the 42 KDa fragment of the N-terminal of DNA gyrase homologous to all other type IIA topoisomerases. ... In mathematics, the linking number is a simple invariant for links (i. ...


References

  1. ^ http://www.nasonline.org/site/PageServer?pagename=AWARDS_molbio]
  • Champoux JJ (2001) DNA Topoisomerases: Structure, Function, and Mechanism Annual Review of Biochemistry 70: 369-413[1]

See also

DNA topology is the focus of a subdiscipline within molecular biology and as a term refers to both the knot-like arrangements that segments of DNA may assume and to the mathematics that pertains to them. ... It has been suggested that this article or section be merged with Superhelix. ...

External links


  Results from FactBites:
 
Pea DNA Topoisomerase I Is Phosphorylated and Stimulated by Casein Kinase 2 and Protein Kinase C -- Tuteja et al. 132 ... (4160 words)
In vitro phosphorylation of pea DNA topoisomerase I by endogenous kinases and its dephosphorylation.
Pea topoisomerase I is phosphorylated at Ser residue(s).
The phosphorylation of pea topoisomerase I by endogenous
SciMedWeb® - DNA TOPOISOMERASE II ALPHA (1185 words)
Topoisomerase II from eukaryotic cells catalyzes the relaxation of supercoiled DNA molecules, catenation, decatenation, knotting and unknotting of circular DNA (Watt P.M. and Hickson I.D., 1994).
Because up-regulation of topo II alpha in vitro and in clinical specimens is associated with increased response to doxorubicin (presumptively by an increase in drug substrate), this may be the mechanism of the increased sensitivity to doxorubicin seen in c-erb-B2-transfected cells (Harris L.N. et al., 1998).
Topoisomerase II-alpha nuclear immunoreactivity (median 14% of nuclei; range 2-62%) was detected in all tumours with highly variable intertumour and intratumour nuclear reactivity.
  More results at FactBites »

 
 

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