Nucl._Acids_Res.-2010-VĂ¡rnai-4163-72.pdf (6.32 MB)
Differential stability of DNA crossovers in solution mediated by divalent cations
journal contribution
posted on 2023-06-08, 07:10 authored by Peter Varnai, Youri TimsitThe assembly of DNA duplexes into higher-order structures plays a major role in many vital cellular functions such as recombination, chromatin packaging and gene regulation. However, little is currently known about the molecular structure and stability of direct DNADNA interactions that are required for such functions. In nature, DNA helices minimize electrostatic repulsion between double helices in several ways. Within crystals, B-DNA forms either right-handed crossovers by groovebackbone interaction or left-handed crossovers by groovegroove juxtaposition. We evaluated the stability of such crossovers at various ionic concentrations using large-scale atomistic molecular dynamics simulations. Our results show that right-handed DNA crossovers are thermodynamically stable in solution in the presence of divalent cations. Attractive forces at short-range stabilize such crossover structures with inter-axial separation of helices less than 20 . Right-handed crossovers, however, dissociate swiftly in the presence of monovalent ions only. Surprisingly, left-handed crossovers, assembled by sequence-independent juxtaposition of the helices, appear unstable even at the highest concentration of Mg2+studied here. Our study provides new molecular insights into chiral association of DNA duplexes and highlights the unique role divalent cations play in differential stabilization of crossover structures. These results may serve as a rational basis to understand the role DNA crossovers play in biological processes.
History
Publication status
- Published
File Version
- Published version
Journal
Nucleic Acids ResearchISSN
0305-1048Publisher
Oxford JournalsExternal DOI
Issue
12Volume
38Page range
4163-4172Pages
10.0Department affiliated with
- Chemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-08-17Usage metrics
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