Topoisomerase: Difference between revisions

Revision as of 00:37, 10 February 2025

Topoisomerase

Topoisomerases are enzymes that participate in the overwinding or underwinding of DNA. The winding problem of DNA arises due to the intertwined nature of its double-helical structure. During processes such as DNA replication and transcription, the DNA helix must be unwound, which can lead to supercoiling. Topoisomerases resolve these topological issues by inducing transient breaks in the DNA strands, allowing them to be untangled or relaxed.

Types of Topoisomerases

Topoisomerases are classified into two main types based on their mechanism of action:

Type I Topoisomerases

Type I topoisomerases cut one of the two strands of DNA, allowing the uncut strand to pass through the break before resealing the cut. This process changes the linking number of the DNA by one. Type I topoisomerases are further divided into Type IA and Type IB, each with distinct mechanisms and structural features.

Type II Topoisomerases

Type II topoisomerases cut both strands of the DNA helix simultaneously, allowing another segment of the double helix to pass through the break. This changes the linking number by two. These enzymes are essential for processes such as chromosome segregation during cell division.

Mechanism of Action

Topoisomerases function through a series of steps involving DNA cleavage, passage, and religation. The catalytic mechanism involves the formation of a transient covalent bond between the enzyme and the DNA, which facilitates the controlled breakage and rejoining of DNA strands.

Biological Functions

Topoisomerases play critical roles in various cellular processes:

DNA Replication: They prevent the overwinding of DNA ahead of the replication fork.
Transcription: They resolve supercoils generated during the transcription of DNA into RNA.
Chromosome Condensation: They are involved in the condensation and decondensation of chromosomes during cell division.

Inhibitors and Poisons

Topoisomerase inhibitors are important tools in cancer therapy. They interfere with the enzyme's ability to manage DNA topology, leading to DNA damage and cell death.

Bacterial Topoisomerase Poisons

These compounds target bacterial topoisomerases, making them effective antibiotics. Examples include quinolones and fluoroquinolones.

Eukaryotic Topoisomerase Inhibitors

In eukaryotes, topoisomerase inhibitors are used in chemotherapy. Drugs such as etoposide and doxorubicin target topoisomerase II, while camptothecin targets topoisomerase I.

DNA Damage and Repair

Topoisomerase activity can lead to DNA double-strand breaks (DSBs), which are repaired by cellular mechanisms such as non-homologous end joining (NHEJ).

Related Pages

References

@@ Line 1: / Line 1: @@
-'''Topoisomerase''' is an enzyme that alters the supercoiling of double-stranded DNA. It is crucial in DNA replication and transcription, as it solves the problem of DNA supercoiling that occurs during these processes. There are two types of topoisomerases: [[Type I topoisomerase|Type I]] and [[Type II topoisomerase|Type II]], which are further divided into subtypes.
+== Topoisomerase ==
-== Function ==
+[[File:Overview_of_DNA_topology.tif|thumb|Overview of DNA topology]]
-Topoisomerases are essential for the survival of the cell. They control and alter the topologic states of DNA by creating transient breaks in the DNA molecule and then rejoining them. This allows them to control the degree of supercoiling of the DNA, which is crucial during DNA replication and transcription.
-== Types ==
+'''Topoisomerases''' are enzymes that participate in the overwinding or underwinding of [[DNA]]. The winding problem of DNA arises due to the intertwined nature of its double-helical structure. During processes such as [[DNA replication]] and [[transcription]], the DNA helix must be unwound, which can lead to supercoiling. Topoisomerases resolve these topological issues by inducing transient breaks in the DNA strands, allowing them to be untangled or relaxed.
-There are two types of topoisomerases: Type I and Type II.
-=== Type I ===
+== Types of Topoisomerases ==
-[[Type I topoisomerase|Type I topoisomerases]] cut one strand of the DNA and relax the supercoiling. They are further divided into two subtypes: Type IA and Type IB.
-==== Type IA ====
+Topoisomerases are classified into two main types based on their mechanism of action:
-[[Type IA topoisomerase|Type IA topoisomerases]] bind to single-stranded DNA and pass the other strand through the break.
-==== Type IB ====
+=== Type I Topoisomerases ===
-[[Type IB topoisomerase|Type IB topoisomerases]] bind to double-stranded DNA and pass one strand through the break.
-=== Type II ===
+[[File:Topo_IA_catalytic_cycle_Illustration.png|thumb|Type I topoisomerase catalytic cycle]]
-[[Type II topoisomerase|Type II topoisomerases]] cut both strands of the DNA and change the linking number by two in each enzymatic step. They are further divided into two subtypes: Type IIA and Type IIB.
-==== Type IIA ====
+Type I topoisomerases cut one of the two strands of DNA, allowing the uncut strand to pass through the break before resealing the cut. This process changes the linking number of the DNA by one. Type I topoisomerases are further divided into Type IA and Type IB, each with distinct mechanisms and structural features.
-[[Type IIA topoisomerase|Type IIA topoisomerases]] include the bacterial DNA gyrase and the eukaryotic topoisomerase II.
-==== Type IIB ====
+=== Type II Topoisomerases ===
-[[Type IIB topoisomerase|Type IIB topoisomerases]] include the archaeal topoisomerase VI.
-== Inhibitors ==
+[[File:Type_II_topoisomerase_catalytic_cycle.png|thumb|Type II topoisomerase catalytic cycle]]
-Topoisomerase inhibitors are used as chemotherapy agents. They work by stabilizing the topoisomerase-DNA cleavage complex, preventing the relegation step of the catalytic cycle which leads to the accumulation of DNA breaks.
-== See also ==
+Type II topoisomerases cut both strands of the DNA helix simultaneously, allowing another segment of the double helix to pass through the break. This changes the linking number by two. These enzymes are essential for processes such as [[chromosome segregation]] during [[cell division]].
-* [[DNA gyrase]]
-* [[Topoisomerase inhibitor]]
+== Mechanism of Action ==
-* [[DNA supercoiling]]
+Topoisomerases function through a series of steps involving DNA cleavage, passage, and religation. The catalytic mechanism involves the formation of a transient covalent bond between the enzyme and the DNA, which facilitates the controlled breakage and rejoining of DNA strands.
+[[File:Catalytic_mechanisms_of_Topoisomerases.png|thumb|Catalytic mechanisms of topoisomerases]]
+== Biological Functions ==
+Topoisomerases play critical roles in various cellular processes:
+* '''DNA Replication''': They prevent the overwinding of DNA ahead of the replication fork.
+* '''Transcription''': They resolve supercoils generated during the transcription of DNA into RNA.
+* '''Chromosome Condensation''': They are involved in the condensation and decondensation of chromosomes during cell division.
+[[File:Topological_ramifications_of_DNA_replication_and_transcription.jpg|thumb|Topological ramifications of DNA replication and transcription]]
+== Inhibitors and Poisons ==
+Topoisomerase inhibitors are important tools in cancer therapy. They interfere with the enzyme's ability to manage DNA topology, leading to DNA damage and cell death.
+=== Bacterial Topoisomerase Poisons ===
+[[File:Bacterial_topoisomerase_poisons.png|thumb|Bacterial topoisomerase poisons]]
+These compounds target bacterial topoisomerases, making them effective antibiotics. Examples include [[quinolones]] and [[fluoroquinolones]].
+=== Eukaryotic Topoisomerase Inhibitors ===
+[[File:Eukaryotic_topoisomerase_poisons_and_inhibitors.png|thumb|Eukaryotic topoisomerase poisons and inhibitors]]
+In eukaryotes, topoisomerase inhibitors are used in chemotherapy. Drugs such as [[etoposide]] and [[doxorubicin]] target topoisomerase II, while [[camptothecin]] targets topoisomerase I.
+== DNA Damage and Repair ==
+Topoisomerase activity can lead to DNA double-strand breaks (DSBs), which are repaired by cellular mechanisms such as [[non-homologous end joining]] (NHEJ).
+[[File:DNA_DSB_TOP2B_PARP-1_complex_with_NHEJ_enzymes.jpg|thumb|DNA DSB TOP2B PARP-1 complex with NHEJ enzymes]]
+== Related Pages ==
+* [[DNA replication]]
+* [[Transcription (biology)]]
+* [[Chromosome segregation]]
+* [[Antibiotics]]
+* [[Chemotherapy]]
+== References ==
+{{Reflist}}
-[[Category:DNA]]
 [[Category:Enzymes]]
-[[Category:Chemotherapy]]
+[[Category:DNA replication]]
-{{stub}}
+[[Category:DNA repair]]