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

Danielle O'Donnol, Andrzej Stasiak, Dorothy Buck

Research output: Contribution to journalArticlepeer-review

11 Citations (SciVal)


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).

Original languageEnglish
Pages (from-to)9181-9188
Number of pages8
JournalNucleic Acids Research
Issue number17
Early online date30 Jun 2018
Publication statusPublished - 28 Sept 2018

ASJC Scopus subject areas

  • Genetics


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