Two convergent pathways of DNA knotting in replicating DNA molecules as revealed by θ-curve analysis

Abstract During DNA replication in living cells some DNA knots are inadvertently produced by DNA topoisomerases facilitating progression of replication forks. The types of DNA knots formed are conditioned by the 3D organization of replicating DNA molecules. Therefore, by characterizing formed DNA kn...

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Bibliographic Details
Published in:Nucleic acids research 2018-09, Vol.46 (17), p.9181-9188
Main Authors: O'Donnol, Danielle, Stasiak, Andrzej, Buck, Dorothy
Format: Article
Language:English
Subjects:
DNA Replication - physiology
DNA Topoisomerase IV - metabolism
DNA, Bacterial - chemistry
DNA, Bacterial - genetics
DNA, Bacterial - metabolism
DNA, Circular - chemistry
DNA, Circular - genetics
DNA, Circular - metabolism
DNA, Superhelical - chemistry
DNA, Superhelical - genetics
Escherichia coli - genetics
Nucleic Acid Conformation
Replication Origin - genetics
Stereoisomerism
Structural Biology
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Summary:Abstract During DNA replication in living cells some DNA knots are inadvertently produced by DNA topoisomerases facilitating progression of replication forks. The types of DNA knots formed are conditioned by the 3D organization of replicating DNA molecules. Therefore, by characterizing formed DNA knots it is possible to infer the 3D arrangement of replicating DNA molecules. This topological inference method is highly developed for knotted DNA circles. However, partially replicated DNA molecules have the form of θ-curves. In this article, we use mathematical formalism of θ-curves to characterize the full possibilities of how knotting can occur during replication of DNA molecules in vivo. To do this, we reanalyze earlier experimental studies of knotted, partially replicated DNA molecules and the previously proposed pathway of their formation. We propose a general model of knotting in replication intermediates, and demonstrate that there is an additional, equally important, parallel knotting pathway that also explains how DNA topoisomerases can produce experimentally observed knotted θ-curves. Interestingly, both pathways require intertwining of freshly replicated sister duplexes (precatenanes).
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gky559