The Structure of Supercoiled Intermediates in DNA Replication

Peter, Brian J.; Ullsperger, Chris; Hiasa, Hiroshi; Marians, Kenneth J.; Cozzarelli, Nicholas R.

doi:10.1016/s0092-8674(00)81740-7

Cited by 165 publications

(163 citation statements)

References 33 publications

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“…In contrast to underwinding, overwinding dramatically increases the difficulty of separating duplex DNA into individual strands. Therefore, accumulation of positive supercoils presents a formidable block to replication, transcription, and other essential DNA processes [5,[7][8][9][10].…”

Section: Dna Topologymentioning

confidence: 99%

DNA topoisomerase II, genotoxicity, and cancer

McClendon

Osheroff

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

363

466

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Type II topoisomerases are ubiquitous enzymes that play essential roles in a number of fundamental DNA processes. They regulate DNA under-and overwinding, and resolve knots and tangles in the genetic material by passing an intact double helix through a transient double-stranded break that they generate in a separate segment of DNA. Because type II topoisomerases generate DNA strand breaks as a requisite intermediate in their catalytic cycle, they have the potential to fragment the genome every time they function. Thus, while these enzymes are essential to the survival of proliferating cells, they also have significant genotoxic effects. This latter aspect of type II topoisomerase has been exploited for the development of several classes of anticancer drugs that are widely employed for the clinical treatment of human malignancies. However, considerable evidence indicates that these enzymes also trigger specific leukemic chromosomal translocations. In light of the impact, both positive and negative, of type II topoisomerases on human cells, it is important to understand how these enzymes function and how their actions can destablize the genome. This article discusses both aspects of human type II topoisomerases.

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Section: Dna Topologymentioning

confidence: 99%

DNA topoisomerase II, genotoxicity, and cancer

McClendon

Osheroff

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

363

466

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“…In general, enzymatic processes that do not cut the DNA backbone do not alter the global topology of DNA; nonetheless, changes in local topology affect enzymatic processes. For example, replication generates local positive supercoiling ahead of the DNA polymerase due to the separation of the duplex DNA by DNA replication helicases (Lohman and Bjornson 1996) and the formation of links, or pre-catenanes, between the two daughter strands behind the polymerase due to the backward diffusion of accumulating positive supercoils via the rotation of the replication fork (Peter et al 1998). If the local positive supercoiling and precatenanes are not resolved, replication or cell division will fail.…”

Section: Dna Topologymentioning

confidence: 99%

The dynamic interplay between DNA topoisomerases and DNA topology

Seol

Neuman

2016

Biophys Rev

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Topological properties of DNA influence its structure and biochemical interactions. Within the cell, DNA topology is constantly in flux. Transcription and other essential processes, including DNA replication and repair, not only alter the topology of the genome but also introduce additional complications associated with DNA knotting and catenation. These topological perturbations are counteracted by the action of topoisomerases, a specialized class of highly conserved and essential enzymes that actively regulate the topological state of the genome. This dynamic interplay among DNA topology, DNA processing enzymes, and DNA topoisomerases is a pervasive factor that influences DNA metabolism in vivo. Building on the extensive structural and biochemical characterization over the past four decades that has established the fundamental mechanistic basis of topoisomerase activity, scientists have begun to explore the unique roles played by DNA topology in modulating and influencing the activity of topoisomerases. In this review we survey established and emerging DNA topology-dependent protein-DNA interactions with a focus on in vitro measurements of the dynamic interplay between DNA topology and topoisomerase activity.

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“…3A). TnpI is also able to catalyse multiple rounds of recombination on catenanes and knots, the interlinked structure of which resembles that of replication intermediates (Peter et al, 1998).…”

Section: Relaxed Recombination and Partial Selectivitymentioning

confidence: 99%

Self‐control in DNA site‐specific recombination mediated by the tyrosine recombinase TnpI

Vanhooff

Galloy

Agaisse

et al. 2006

Molecular Microbiology

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SummaryTn 4430 is a distinctive transposon of the Tn 3 family that encodes a tyrosine recombinase (TnpI) to resolve replicative transposition intermediates. The internal resolution site of Tn 4430 (IRS, 116 bp) contains two inverted repeats (IR1 and IR2) at the crossover core site, and two additional TnpI binding motifs (DR1 and DR2) adjacent to the core. Deletion analysis demonstrated that DR1 and DR2 are not required for recombination in vivo and in vitro . Their function is to provide resolution selectivity to the reaction by stimulating recombination between directly oriented sites on a same DNA molecule. In the absence of DR1 and/ or DR2, TnpI-mediated recombination of supercoiled DNA substrates gives a mixture of topologically variable products, while deletion between two wild-type IRSs exclusively produces two-noded catenanes. This demonstrates that TnpI binding to the accessory motifs DR1 and DR2 contributes to the formation of a specific synaptic complex in which catalytically inert recombinase subunits act as architectural elements to control recombination sites pairing and strand exchange. A model for the organization of TnpI/IRS recombination complex is presented.

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The Structure of Supercoiled Intermediates in DNA Replication

Cited by 165 publications

References 33 publications

DNA topoisomerase II, genotoxicity, and cancer

DNA topoisomerase II, genotoxicity, and cancer

The dynamic interplay between DNA topoisomerases and DNA topology

Self‐control in DNA site‐specific recombination mediated by the tyrosine recombinase TnpI

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