Deinococcus radiodurans HU: a versatile architect of nucleoid structure and plasticity

Nucleoid-associated proteins are known to compact and organise bacterial genomes, but how their local DNA binding shapes higher-order chromatin architecture remains unclear. Using in vitro and in situ approaches, we investigated how Deinococcus radiodurans HU (DrHU) orchestrates nucleoid organisation. DrHU engages DNA through two synergistic binding modes: high-affinity β-hairpin-mediated stabilisation of DNA loops and low-affinity, multivalent interaction via its N-terminal tail, driving parallel, uniformly spaced DNA alignment. In vitro, DrHU organises supercoiled plasmid DNA into regular 2D lattices of double-spirals, while in situ, UV-C light induces a nucleoid transition from a loose DNA mesh to a blue liquid crystalline phase characterised by DNA swirls. The striking structural similarity and shared inter-filament spacing of these two arrangements suggests that DrHU plays a pivotal role in genome organisation through its versatile binding properties that enable DNA loop stabilisation, protection and DNA bridging, linking molecular interactions to 3D genome ordering and stress-induced remodelling.