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 ◽  
...  

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.

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 868 ◽  
Author(s):  
Morimoto ◽  
Tsuda ◽  
Bunch ◽  
Sasanuma ◽  
Austin ◽  
...  

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.


Polymers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1126 ◽  
Author(s):  
Dusan Racko ◽  
Fabrizio Benedetti ◽  
Dimos Goundaroulis ◽  
Andrzej Stasiak

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.


2007 ◽  
Vol 35 (15) ◽  
pp. 5223-5231 ◽  
Author(s):  
Y. Burnier ◽  
C. Weber ◽  
A. Flammini ◽  
A. Stasiak

2001 ◽  
Vol 98 (6) ◽  
pp. 3045-3049 ◽  
Author(s):  
A. V. Vologodskii ◽  
W. Zhang ◽  
V. V. Rybenkov ◽  
A. A. Podtelezhnikov ◽  
D. Subramanian ◽  
...  

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

2010 ◽  
Vol 38 (2) ◽  
pp. 438-442 ◽  
Author(s):  
Andrew D. Bates ◽  
Anthony Maxwell

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.


Author(s):  
Giovanni Capranico ◽  
Monica Binaschi ◽  
Maria E. Borgnetto ◽  
Franco Zunino ◽  
Mariagrazia Cornarotti ◽  
...  

2002 ◽  
Vol 132 (3) ◽  
pp. 409-416 ◽  
Author(s):  
A. Sakaguchi ◽  
M. Miyaike ◽  
K. Kuroda ◽  
N. Nozaki ◽  
M. Tanaka ◽  
...  

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