Pathways of DNA unlinking: A story of stepwise simplification.

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.

New biologically motivated knot table.

The knot nomenclature in common use, summarized in Rolfsen's knot table [Rolfsen (1990) Knots and Links, American Mathematical Society], was not originally designed to distinguish between mirror images. This ambiguity is particularly inconvenient when studying knotted biopolymers such as DNA and proteins, since their chirality is often significant. In the present article, we propose a biologically meaningful knot table where a representative of a chiral pair is chosen on the basis of its mean writhe. There is numerical evidence that the sign of the mean writhe is invariant for each knot in a chiral pair. We review numerical evidence where, for each knot type K, the mean writhe is taken over a large ensemble of randomly chosen realizations of K. It has also been proposed that a chiral pair can be distinguished by assessing the writhe of a minimal or ideal conformation of the knot. In all cases examined to date, the two methods produce the same results.