In vivo evidence of alternative loop geometries in DNA-protein complexes

TL;DR

This study provides in vivo evidence that DNA-protein looping involves two distinct DNA conformations, explaining complex free energy oscillations and asymmetries observed in biological systems.

Contribution

It introduces the concept of dual DNA conformations as an explanation for in vivo looping free energy behavior, advancing understanding of DNA-protein interactions.

Findings

Two conformations have different free energy minima.

Distinct conformations respond differently to architectural proteins.

The model accurately explains oscillatory free energy patterns.

Abstract

The in vivo free energy of looping double-stranded DNA by the lac repressor has a remarkable behavior whose origins are not fully understood. In addition to the intrinsic periodicity of the DNA double helix, the in vivo free energy has an oscillatory component of about half the helical period and oscillates asymmetrically with an amplitude significantly smaller than predicted by current theories. Here, we show that the in vivo behavior is accurately accounted for by the simultaneous presence of two distinct conformations of looped DNA. Our analysis reveals that these two conformations have different optimal free energies and phases and that they behave distinctly in the presence of key architectural proteins.