The dynamic interplay between DNA topoisomerases and DNA topology

Seol, Yeonee; Neuman, Keir C.

doi:10.1007/s12551-016-0206-x

Cited by 16 publications

(9 citation statements)

References 131 publications

(178 reference statements)

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“…Indeed, with the focus turning more to enzymatic processes, the dogma shifted and DNA architectural studies were relegated to the realm of interesting in vitro exercises with little physiological significance. Moreover, given the observation that Topoisomerase (Top I and Top II) enzymes were found to relax both positive and negative supercoils, it was thought that DNA stress should not be a feature of normal cells.…”

Section: Transcription Applies Force and Generates Supercoiling Of Dnamentioning

confidence: 99%

DNA Conformation Regulates Gene Expression: The MYC Promoter and Beyond

Zaytseva

Quinn

2018

BioEssays

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Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its regulation. Dissection of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control.

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Section: Transcription Applies Force and Generates Supercoiling Of Dnamentioning

confidence: 99%

DNA Conformation Regulates Gene Expression: The MYC Promoter and Beyond

Zaytseva

Quinn

2018

BioEssays

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“…Topological changes in DNA are accomplished by type I topoisomerases, which act by generation of single-strand breaks, and type II enzymes, which accomplish topological transformations via double-strand breaks. There is a wealth of information concerning the biochemical properties of these enzymes, and recent reviews include mechanisms of type 1A enzymes that use a strand passage mechanism ( Dekker et al, 2002 ; Dasgupta et al, 2020 ), type 1B topoisomerases ( Champoux, 2001 ; Pommier et al, 2016 ; Seol and Neuman, 2016 ), and type II enzymes ( Vos et al, 2011 ; Chen et al, 2013 ; Bush et al, 2015 ; Hauk and Berger, 2016 ). The DNA cleavage mechanisms of topoisomerases are summarized in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases

Sun

Nitiss

Pommier

2022

Front. Mol. Biosci.

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Topoisomerases play crucial roles in DNA metabolism that include replication, transcription, recombination, and chromatin structure by manipulating DNA structures arising in double-stranded DNA. These proteins play key enzymatic roles in a variety of cellular processes and are also likely to play structural roles. Topoisomerases allow topological transformations by introducing transient breaks in DNA by a transesterification reaction between a tyrosine residue of the enzyme and DNA. The cleavage reaction leads to a unique enzyme intermediate that allows cutting DNA while minimizing the potential for damage-induced genetic changes. Nonetheless, topoisomerase-mediated cleavage has the potential for inducing genome instability if the enzyme-mediated DNA resealing is impaired. Regulation of topoisomerase functions is accomplished by post-translational modifications including phosphorylation, polyADP-ribosylation, ubiquitylation, and SUMOylation. These modifications modulate enzyme activity and likely play key roles in determining sites of enzyme action and enzyme stability. Topoisomerase-mediated DNA cleavage and rejoining are affected by a variety of conditions including the action of small molecules, topoisomerase mutations, and DNA structural forms which permit the conversion of the short-lived cleavage intermediate to persistent topoisomerase DNA–protein crosslink (TOP-DPC). Recognition and processing of TOP-DPCs utilizes many of the same post-translational modifications that regulate enzyme activity. This review focuses on SUMOylation of topoisomerases, which has been demonstrated to be a key modification of both type I and type II topoisomerases. Special emphasis is placed on recent studies that indicate how SUMOylation regulates topoisomerase function in unperturbed cells and the unique roles that SUMOylation plays in repairing damage arising from topoisomerase malfunction.

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“…Most FQ-resistant mutants also exhibited CS toward tetracycline and chloramphenicol, consistent with results in E. faecalis ( 7 ). FQ resistance mutations in gyrA and parC result in three-dimensional structural changes of the DNA gyrase and the topoisomerase IV that are associated with the modification of DNA topology altering the global supercoiling of the bacterial genome ( 25 ). In Salmonella enterica serovar Typhimurium ( 26 ), this leads to an altered transcriptome and the subsequent global reprogramming of gene expression ( 27 , 28 ), which in turn leads to collateral effects.…”

Section: Discussionmentioning

confidence: 99%

Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone resistance evolution

Liakopoulos

Aulin

Buffoni

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance A promising strategy to overcome the evolution of antibiotic-resistant bacteria is to use collateral sensitivity-informed antibiotic treatments that rely on cycling or mixing of antibiotics, such that that resistance toward one antibiotic confers increased sensitivity to the other. Here, focusing on multistep fluoroquinolone resistance in Streptococcus pneumoniae , we show that antibiotic resistance induces diverse collateral responses whose magnitude and direction are determined by allelic identity. Using mathematical simulations, we show that these effects can be exploited via combination treatment regimens to suppress the de novo emergence of resistance during treatment.

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The dynamic interplay between DNA topoisomerases and DNA topology

Cited by 16 publications

References 131 publications

DNA Conformation Regulates Gene Expression: The MYC Promoter and Beyond

DNA Conformation Regulates Gene Expression: The MYC Promoter and Beyond

SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases

Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone resistance evolution

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