Phase behaviour of DNA in presence of DNA-binding proteins

TL;DR

This study models the phase behavior of DNA in the presence of binding proteins, revealing biphasic regimes and structural states of dense DNA phases, relevant to biological processes like DNA condensation and transcription factories.

Contribution

The paper introduces a thermodynamic model combining Flory-Huggins theory and Hamiltonian paths to analyze DNA-protein interactions and phase behavior, highlighting the influence of ionic strength on DNA structure.

Findings

DNA exhibits biphasic phase behavior with dense and dilute phases.

Dense DNA phases can be molten globules or crystalline, depending on bending rigidity.

The model aligns with biological processes like DNA condensation and transcription factories.

Abstract

To characterize the thermodynamical equilibrium of DNA chains interacting with a solution of non-specific binding proteins, a Flory-Huggins free energy model was implemented. We explored the dependence on DNA and protein concentrations of the DNA collapse. For physiologically relevant values of the DNA-protein affinity, this collapse gives rise to a biphasic regime with a dense and a dilute phase; the corresponding phase diagram was computed. Using an approach based on Hamiltonian paths, we show that the dense phase has either a molten globule or a crystalline structure, depending on the DNA bending rigidity, which is influenced by the ionic strength. These results are valid at the thermodynamical equilibrium and should therefore be consistent with many biological processes, whose characteristic timescales range typically from 1 ms to 10 s. Our model may thus be applied to biological phenomena that involve DNA-binding proteins, such as DNA condensation with crystalline order, which occurs in some bacteria to protect their chromosome from detrimental factors; or transcription initiation, which occurs in clusters called transcription factories that are reminiscent of the dense phase characterized in this study.