Theory on the mechanism of DNA renaturation: Stochastic nucleation and zipping

TL;DR

This paper presents a stochastic dynamical model of DNA renaturation, highlighting the roles of incorrect-contact formation, nucleation, and zipping, and explaining how these steps influence the overall renaturation rate.

Contribution

It introduces a detailed three-step model distinguishing nucleation and zipping, improving understanding of DNA renaturation mechanisms beyond previous two-state models.

Findings

Square-root dependency of renaturation rate on DNA length

Inverse scaling of rate with medium viscosity

Inverse scaling of rate with sequence complexity

Abstract

Renaturation of complementary single strands of DNA is one of the important processes that requires better understanding in the view of molecular biology and biological physics. Here we develop a stochastic dynamical model on the DNA renaturation. According to our model there are at least three steps in the renaturation process viz. incorrect-contact formation, correct-contact formation and nucleation, and zipping. Most of the earlier two-state models combined nucleation with incorrect-contact formation step. In our model we suggest that it is considerably meaningful when we combine the nucleation with the zipping since nucleation is the initial step of zipping and the nucleated and zipping molecules are indistinguishable. Incorrect-contact formation step is a pure three-dimensional diffusion controlled collision process. Whereas nucleation involves several rounds of one-dimensional slithering dynamics of one single strand of DNA on the other complementary strand in the process of searching for the correct-contact and then initiate nucleation. Upon nucleation, the stochastic zipping follows to generate a fully renatured double stranded DNA. It seems that the square-root dependency of the overall renaturation rate constant on the length of reacting single strands originates mainly from the geometric constraints in the diffusion controlled incorrect-contact formation step. Further the inverse scaling of the renaturation rate on the viscosity of the reaction medium also originates from the incorrect-contact formation step. On the other hand the inverse scaling of the renaturation rate with the sequence complexity originates from the stochastic zipping which involves several rounds of crossing over the free-energy barrier at microscopic levels.