Topoisomerase

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Topoisomerases
Identifier
External IDs
  • CAS number : 80449-01-0
  • CAS number: 142805-56-9 (Type II)
Enzyme classification
EC, category 5.6.2.- isomerase
Response type Introduction of double strand breaks , passing a strand through the gap that has arisen, reuniting the strands
Substrate DNA

Topoisomerases are enzymes responsible for changes in the topology of DNA - molecules are responsible, which at a supercoiling necessary. A distinction is made between two superordinate classes:

Type I topoisomerase

Function of topoisomerase I in bacteria:

The bacterial topoisomerase I can only relax negative supercoiling . It needs magnesium ions for its activity. Prokaryotic topoisomerases I bind covalently to the 5 'end of the strand break by means of a phosphotyrosine bond. This conserves the energy of the broken bond and allows the two ends to be reconnected after topoisomerization. The enzyme does not need any energy in the form of ATP to function .

Function of topoisomerase I in eukaryotes:

The eukaryotic topoisomerase I relaxes both positively and negatively supercoiled DNA. It binds to the 5'-end (phosphate residue) of the strand break by means of the hydroxyl group of a tyrosine residue and causes the 3'-segments to rotate.

Due to the de-spiraling of the DNA segments that have just been read, which is necessary for the processes of transcription and replication, positive supercoiling occurs automatically in adjacent areas of the helix , an excessive twisting of the DNA double helix, which is associated with torsional forces. To counteract the torsional forces, the positive supercoiling is relaxed by the eukaryotic topoisomerase type I. The topoisomerase type I causes a single-strand break without consuming ATP. When it leaves the DNA, it closes the break again. The topoisomerase I & IV then remove the negative deviations in the twisted state and thus restore the normal physiological state.

Topoisomerase type II

Main article : Type II topoisomerase

Function of topoisomerase II in bacteria:

The bacterial topoisomerase II causes negative supercoiling of the DNA. This allows it to relax positively supercoiled DNA and introduce negative twist into relaxed DNA. To do this, it induces double strand breaks; the negative supercoiling occurs with the consumption of ATP.

Function of the eukaryotic topoisomerase II alpha:

Eukaryotic topoisomerase II alpha can relax positive and negative supercoiling by means of a double-strand break while consuming ATP.

Type II topoisomerases counteract the above-mentioned torsional forces and influence the spatial arrangement of the DNA. With the consumption of ATP, they create a temporary DNA double-strand break so that an adjacent part of the helix can pass through the gap that has formed. This enables extensive chromatin arrangements .

Medical relevance

Antibiotics from the family of gyrase inhibitors inhibit topoisomerase II and partially IV. Cytostatics such as irinotecan are among the topoisomerase inhibitors .

Individual evidence

  1. ^ Peter Karlson: Karlsons Biochemie und Pathobiochemie 15th edition, Georg Thieme Verlag, Stuttgart 2005, p. 835.
  2. ^ A b Joachim Rassow: Biochemistry. 2nd edition, Georg Thieme Verlag, Stuttgart 2008, p. 436.
  3. ^ Peter Karlson: Karlsons Biochemie und Pathobiochemie 15th edition, Georg Thieme Verlag, Stuttgart 2005, p. 797.
  4. ^ Rolf Knippers: Molecular Genetics 9th edition, Georg Thieme Verlag, Stuttgart 2006, p. 190.

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