Document Type

Article

Publication Date

1-1-2019

Abstract

The topological state of covalently closed, double-stranded DNA is defined by the knot type $K$ and the linking-number difference $\\Delta Lk$ relative to unknotted relaxed DNA. DNA topoisomerases are essential enzymes that control the topology of DNA in all cells. In particular, type-II topoisomerases change both $K$ and $\\Delta Lk$ by a duplex-strand-passage mechanism and have been shown to simplify the topology of DNA to levels below thermal equilibrium at the expense of ATP hydrolysis. It remains a key question how small enzymes are able to preferentially select strand passages that result in topology simplification in much larger DNA molecules. Using numerical simulations, we consider the non-equilibrium dynamics of transitions between topological states $(K,\\Delta Lk)$ in DNA induced by type-II topoisomerases. For a biological process that delivers DNA molecules in a given topological state $(K,\\Delta Lk)$ at a constant rate we fully characterize the pathways of topology simplification by type-II topoisomerases in terms of stationary probability distributions and probability currents on the network of topological states $(K,\\Delta Lk)$. In particular, we observe that type-II topoisomerase activity is significantly enhanced in DNA molecules that maintain a supercoiled state with constant torsional tension. This is relevant for bacterial cells in which torsional tension is maintained by enzyme-dependent homeostatic mechanisms such as DNA-gyrase activity.

Comments

© 2019, Oxford University Press. Original published version available at https://doi.org/10.1093/nar/gky1174

First Page

69

Last Page

84

Publication Title

Oxford University Press

DOI

10.1093/nar/gky1174

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