1. Pathways of DNA unlinking: A story of stepwise simplification
- Author
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Mariel Vazquez, Reuben Brasher, Michelle Flanner, Koya Shimokawa, Kai Ishihara, Robert Stolz, David J. Sherratt, and Masaaki Yoshida
- Subjects
0301 basic medicine ,Models, Molecular ,Computer science ,lcsh:Medicine ,01 natural sciences ,chemistry.chemical_compound ,Models ,lcsh:Science ,Link (knot theory) ,Topology (chemistry) ,Recombination, Genetic ,0303 health sciences ,Multidisciplinary ,biology ,Escherichia coli Proteins ,Bacterial ,Chromosomes, Bacterial ,Monomer ,DNA, Bacterial ,DNA Replication ,Computational biology ,Network topology ,Article ,Chromosomes ,03 medical and health sciences ,Genetic ,Escherichia coli ,0101 mathematics ,030304 developmental biology ,Topological complexity ,Markov chain ,Integrases ,business.industry ,Topoisomerase ,lcsh:R ,010102 general mathematics ,Escherichia coli DNA ,Chromosome ,Membrane Proteins ,Molecular ,DNA ,Replication (computing) ,Recombination ,030104 developmental biology ,chemistry ,biology.protein ,lcsh:Q ,Artificial intelligence ,business - Abstract
In Escherichia coli DNA replication yields interlinked chromosomes. Controlling topological changes associated with replication and returning the newly replicated chromosomes to an unlinked monomeric state is essential to cell survival. In the absence of the topoisomerase topoIV, the site-specific recombination complex XerCD- dif-FtsK can remove replication links by local reconnection. We previously showed mathematically that there is a unique minimal pathway of unlinking replication links by reconnection while stepwise reducing the topological complexity. However, the possibility that reconnection preserves or increases topological complexity is biologically plausible. In this case, are there other unlinking pathways? Which is the most probable? We consider these questions in an analytical and numerical study of minimal unlinking pathways. We use a Markov Chain Monte Carlo algorithm with Multiple Markov Chain sampling to model local reconnection on 491 different substrate topologies, 166 knots and 325 links, and distinguish between pathways connecting a total of 881 different topologies. We conclude that the minimal pathway of unlinking replication links that was found under more stringent assumptions is the most probable. We also present exact results on unlinking a 6-crossing replication link. These results point to a general process of topology simplification by local reconnection, with applications going beyond DNA.
- Published
- 2017