Closing the DNA replication cycle: from simple circular molecules to supercoiled and knotted DNA catenanes.

Jorge B Schvartzman,Pablo Hernández,Dora B Krimer,Andrzej Stasiak,Julien Dorier

doi:10.1093/nar/gkz586

Abstract

Due to helical structure of DNA, massive amounts of positive supercoils are constantly introduced ahead of each replication fork. Positive supercoiling inhibits progression of replication forks but various mechanisms evolved that permit very efficient relaxation of that positive supercoiling. Some of these mechanisms lead to interesting topological situations where DNA supercoiling, catenation and knotting coexist and influence each other in DNA molecules being replicated. Here, we first review fundamental aspects of DNA supercoiling, catenation and knotting when these qualitatively different topological states do not coexist in the same circular DNA but also when they are present at the same time in replicating DNA molecules. We also review differences between eukaryotic and prokaryotic cellular strategies that permit relaxation of positive supercoiling arising ahead of the replication forks. We end our review by discussing very recent studies giving a long-sought answer to the question of how slow DNA topoisomerases capable of relaxing just a few positive supercoils per second can counteract the introduction of hundreds of positive supercoils per second ahead of advancing replication forks.

Highlights

Watson and Crick’s ingenious inference that DNA forms a double-stranded helix with about 10 base pair per turn has immediately posed the questions of how DNA strands are separated during DNA replication without encountering topological difficulties [1]
The preferential action on positively supercoiled DNA, forming left-handed superhelices makes that topoisomerase IV (topo IV) can partially substitute gyrase in its role of relaxation of positive supercoiling generated during DNA replication [37]
Two-thirds of a century after Watson and Crick considered topological difficulties connected to replication of helical DNA molecules [1], we have a general understanding of how DNA topoisomerases make it possible that DNA replication proceeds without everything getting tangled

Summary

Introduction

Watson and Crick’s ingenious inference that DNA forms a double-stranded helix with about 10 base pair per turn has immediately posed the questions of how DNA strands are separated during DNA replication without encountering topological difficulties [1]. The action of either type I or type II DNA topoisomerases on yet unreplicated portions of replicating DNA molecules permits the relaxation of torsional stress generated by strand separation.

Results

Conclusion