Compaction of bacterial genomic DNA: Clarifying the concepts

TL;DR

This review analyzes various physical mechanisms behind bacterial DNA compaction, comparing experimental and simulation data to clarify their roles and highlight areas needing further research.

Contribution

It systematically evaluates and clarifies the physical principles of DNA compaction mechanisms, emphasizing the potential importance of phase separation and protein self-association.

Findings

Supercoiling and DNA-bridging proteins may be overestimated.

Segregative phase separation could play a significant role.

Synergistic mechanisms deserve more investigation.

Abstract

The unconstrained genomic DNA of bacteria forms a coil, which volume exceeds 1000 times the volume of the cell. Since prokaryotes lack a membrane-bound nucleus, in sharp contrast with eukaryotes, the DNA may consequently be expected to occupy the whole available volume when constrained to fit in the cell. Still, it has been known for more than half a century that the DNA is localized in a well defined region of the cell, called the nucleoid, which occupies only 15% to 25% of the total volume. Although this problem has focused the attention of many scientists for the past decades, there is still no certainty concerning the mechanism that enables such a dramatic compaction. The goal of this Topical Review is to take stock of our knowledge on this question by listing all possible compaction mechanisms with the proclaimed desire to clarify the physical principles they are based upon and discuss them in the light of experimental results and the results of simulations based on coarse-grained models. In particular, the fundamental differences between psi-condensation and segregative phase separation and between the condensation by small and long polycations are highlighted. This review suggests that the importance of certain mechanisms, like supercoiling and the architectural properties of DNA-bridging and DNA-bending nucleoid proteins, may have been overestimated, whereas other mechanisms, like segregative phase separation and the self-association of nucleoid proteins, as well as the possible role of the synergy of two or more mechanisms, may conversely deserve more attention.