Electrostatics of DNA-DNA juxtapositions

Consequences for type II topoisomerase function

Graham L. Randall, Bernard Pettitt, Gregory R. Buck, E. Lynn Zechiedrich

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Type II topoisomerases resolve problematic DNA topologies such as knots, catenanes, and supercoils that arise as a consequence of DNA replication and recombination. Failure to remove problematic DNA topologies prohibits cell division and can result in cell death or genetic mutation. Such catastrophic consequences make topoisomerases an effective target for antibiotics and anticancer agents. Despite their biological and clinical importance, little is understood about how a topoisomerase differentiates DNA topologies in a molecule that is significantly larger than the topoisomerase itself. It has been proposed that type II topoisomerases recognize angle and curvature between two DNA helices characteristic of knotted and catenated DNA to account for the enzyme's preference to unlink instead of link DNA. Here we consider the electrostatic potential of DNA juxtapositions to determine the possibility of juxtapositions occurring through Brownian diffusion. We found that despite the large negative electrostatic potential formed between two juxtaposed DNA helices, a bulk counterion concentration as small as 50 mM provides sufficient electrostatic screening to prohibit significant interaction beyond an interhelical separation of 3 nm in both hooked and free juxtapositions. This suggests that instead of electrostatics, mechanical forces such as those occurring in anaphase, knots, catenanes, or the writhe of supercoiled DNA may be responsible for the formation of DNA juxtapositions.

Original languageEnglish
JournalJournal of Physics Condensed Matter
Volume18
Issue number14
DOIs
StatePublished - Apr 12 2006
Externally publishedYes

Fingerprint

Type II DNA Topoisomerase
Electrostatics
DNA
deoxyribonucleic acid
electrostatics
Catenanes
Topology
Catenated DNA
topology
helices
Superhelical DNA
Type I DNA Topoisomerase
Cell death
cell division
Antineoplastic Agents
antibiotics
Screening
Antibiotics
mutations
Cells

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Electronic, Optical and Magnetic Materials

Cite this

Electrostatics of DNA-DNA juxtapositions : Consequences for type II topoisomerase function. / Randall, Graham L.; Pettitt, Bernard; Buck, Gregory R.; Zechiedrich, E. Lynn.

In: Journal of Physics Condensed Matter, Vol. 18, No. 14, 12.04.2006.

Research output: Contribution to journalArticle

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