scholarly journals TOP2B: The First Thirty Years

2018 ◽  
Vol 19 (9) ◽  
pp. 2765 ◽  
Author(s):  
Caroline Austin ◽  
Ka Lee ◽  
Rebecca Swan ◽  
Mushtaq Khazeem ◽  
Catriona Manville ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Type Ii ◽  
Dna Duplex ◽  
Topoisomerase Iiα ◽  
Dna Topoisomerase ◽  
Dna Topoisomerases ◽  
Cellular Processes ◽  
Double Stranded Dna ◽  
Type Ii Dna Topoisomerases ◽  
Strand Passage

Type II DNA topoisomerases (EC 5.99.1.3) are enzymes that catalyse topological changes in DNA in an ATP dependent manner. Strand passage reactions involve passing one double stranded DNA duplex (transported helix) through a transient enzyme-bridged break in another (gated helix). This activity is required for a range of cellular processes including transcription. Vertebrates have two isoforms: topoisomerase IIα and β. Topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the 30 years since its discovery.

scholarly journals Type II DNA Topoisomerases Cause Spontaneous Double-Strand Breaks in Genomic DNA

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 868 ◽  
Author(s):  
Morimoto ◽  
Tsuda ◽  
Bunch ◽  
Sasanuma ◽  
Austin ◽  
...  
Keyword(s):  
Double Strand Breaks ◽  
Nonhomologous End Joining ◽  
Type Ii ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Dna Topoisomerase ◽  
Strand Breaks ◽  
Brca1 Brca2 ◽  
Type Ii Dna Topoisomerases ◽  
Strand Passage

Type II DNA topoisomerase enzymes (TOP2) catalyze topological changes by strand passage reactions. They involve passing one intact double stranded DNA duplex through a transient enzyme-bridged break in another (gated helix) followed by ligation of the break by TOP2. A TOP2 poison, etoposide blocks TOP2 catalysis at the ligation step of the enzyme-bridged break, increasing the number of stable TOP2 cleavage complexes (TOP2ccs). Remarkably, such pathological TOP2ccs are formed during the normal cell cycle as well as in postmitotic cells. Thus, this ‘abortive catalysis’ can be a major source of spontaneously arising DNA double-strand breaks (DSBs). TOP2-mediated DSBs are also formed upon stimulation with physiological concentrations of androgens and estrogens. The frequent occurrence of TOP2-mediated DSBs was previously not appreciated because they are efficiently repaired. This repair is performed in collaboration with BRCA1, BRCA2, MRE11 nuclease, and tyrosyl-DNA phosphodiesterase 2 (TDP2) with nonhomologous end joining (NHEJ) factors. This review first discusses spontaneously arising DSBs caused by the abortive catalysis of TOP2 and then summarizes proteins involved in repairing stalled TOP2ccs and discusses the genotoxicity of the sex hormones.

scholarly journals Chromatin Loop Extrusion and Chromatin Unknotting

Polymers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1126 ◽  
Author(s):  
Dusan Racko ◽  
Fabrizio Benedetti ◽  
Dimos Goundaroulis ◽  
Andrzej Stasiak
Keyword(s):  
The State ◽  
Coarse Grained ◽  
Chromatin Loop ◽  
Type Ii ◽  
Genomic Distance ◽  
Dna Topoisomerases ◽  
Chromosome Conformation ◽  
Double Stranded Dna ◽  
Dynamics Simulations ◽  
Type Ii Dna Topoisomerases

It has been a puzzle how decondensed interphase chromosomes remain essentially unknotted. The natural expectation is that in the presence of type II DNA topoisomerases that permit passages of double-stranded DNA regions through each other, all chromosomes should reach the state of topological equilibrium. The topological equilibrium in highly crowded interphase chromosomes forming chromosome territories would result in formation of highly knotted chromatin fibres. However, Chromosome Conformation Capture (3C) methods revealed that the decay of contact probabilities with the genomic distance in interphase chromosomes is practically the same as in the crumpled globule state that is formed when long polymers condense without formation of any knots. To remove knots from highly crowded chromatin, one would need an active process that should not only provide the energy to move the system from the state of topological equilibrium but also guide topoisomerase-mediated passages in such a way that knots would be efficiently unknotted instead of making the knots even more complex. We perform coarse-grained molecular dynamics simulations of the process of chromatin loop extrusion involving knotted and catenated chromatin fibres to check whether chromatin loop extrusion may be involved in active unknotting of chromatin fibres. Our simulations show that the process of chromatin loop extrusion is ideally suited to actively unknot, decatenate and demix chromatin fibres in interphase chromosomes.

scholarly journals Mechanism of topology simplification by type II DNA topoisomerases

2001 ◽  
Vol 98 (6) ◽  
pp. 3045-3049 ◽  
Author(s):  
A. V. Vologodskii ◽  
W. Zhang ◽  
V. V. Rybenkov ◽  
A. A. Podtelezhnikov ◽  
D. Subramanian ◽  
...  
Keyword(s):  
Type Ii ◽  
Dna Topoisomerases ◽  
Type Ii Dna Topoisomerases ◽  
Topology Simplification

DNA crossovers and type II DNA topoisomerases: a thermodynamical study 1 1Edited by T. Richmond

1998 ◽  
Vol 284 (5) ◽  
pp. 1279-1287 ◽  
Author(s):  
Jean-Louis Sikorav ◽  
Bertrand Duplantier ◽  
Gérard Jannink ◽  
Youri Timsit
Keyword(s):  
Type Ii ◽  
Dna Topoisomerases ◽  
Type Ii Dna Topoisomerases

The role of ATP in the reactions of type II DNA topoisomerases

2010 ◽  
Vol 38 (2) ◽  
pp. 438-442 ◽  
Author(s):  
Andrew D. Bates ◽  
Anthony Maxwell
Keyword(s):  
Atp Hydrolysis ◽  
Dna Gyrase ◽  
Dna Topology ◽  
Type Ii ◽  
Free Energies ◽  
Dna Topoisomerases ◽  
Type Ii Dna Topoisomerases ◽  
Topology Simplification ◽  
Hydrolysis Of

Type II DNA topoisomerases catalyse changes in DNA topology in reactions coupled to the hydrolysis of ATP. In the case of DNA gyrase, which can introduce supercoils into DNA, the requirement for free energy is clear. However, the non-supercoiling type II enzymes carry out reactions that are apparently energetically favourable, so their requirement for ATP hydrolysis is not so obvious. It has been shown that many of these enzymes (the type IIA family) can simplify the topology of their DNA substrates to a level beyond that expected at equilibrium. Although this seems to explain their usage of ATP, we show that the free energies involved in topology simplification are very small (<0.2% of that available from ATP) and we argue that topology simplification may simply be an evolutionary relic.

Sequence-specific poisons of type II DNA topoisomerases

1998 ◽  
pp. 7-38 ◽  
Author(s):  
Giovanni Capranico ◽  
Monica Binaschi ◽  
Maria E. Borgnetto ◽  
Franco Zunino ◽  
Mariagrazia Cornarotti ◽  
...  
Keyword(s):  
Type Ii ◽  
Dna Topoisomerases ◽  
Type Ii Dna Topoisomerases

Epitope Distribution of Randomly Established Monoclonal Antibodies against Human Type II DNA Topoisomerases

2002 ◽  
Vol 132 (3) ◽  
pp. 409-416 ◽  
Author(s):  
A. Sakaguchi ◽  
M. Miyaike ◽  
K. Kuroda ◽  
N. Nozaki ◽  
M. Tanaka ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Type Ii ◽  
Dna Topoisomerases ◽  
Human Type ◽  
Type Ii Dna Topoisomerases
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