DNA uptake into nuclei: Numerical and analytical results

TL;DR

This paper combines theoretical estimates and computer simulations to analyze DNA uptake into the nucleus, proposing new interpretations of experimental observations related to entropic repulsion and mechanisms of DNA translocation.

Contribution

It introduces a novel interpretation of DNA translocation dynamics, considering entropic repulsion and potential mechanisms like small forces or ratchet effects.

Findings

Entropic repulsion decreases monotonically during uptake.

DNA can be pulled by a small force or a slow ratchet mechanism.

Slowing down of DNA uptake requires further experimental clarification.

Abstract

The dynamics of polymer translocation through a pore has been the subject of recent theoretical and experimental works. We have considered theoretical estimates and performed computer simulations to understand the mechanism of DNA uptake into the cell nucleus, a phenomenon experimentally investigated by attaching a small bead to the free end of the double helix and pulling this bead with the help of an optical trap. The experiments show that the uptake is monotonous and slows down when the remaining DNA segment becomes very short. Numerical and analytical studies of the entropic repulsion between the DNA filament and the membrane wall suggest a new interpretation of the experimental observations. Our results indicate that the repulsion monotonically decreases as the uptake progresses. Thus, the DNA is pulled in (i) either by a small force of unknown origin, and then the slowing down can be interpreted only statistically; (ii) or by a strong but slow ratchet mechanism, which would naturally explain the observed monotonicity, but then the slowing down requires additional explanations. Only further experiments can unambiguously distinguish between these two mechanisms.