Deinococcus radiodurans has been shown to exhibit a highly compact nucleoid, which may limit dispersion of DNA fragments, thereby facilitating DNA repair processes. Interestingly, following exposure to ionizing or UV radiation, D. radiodurans nucleoids rapidly change their morphology to adopt a “super” compact conformation (unpublished data) and no longer display the diverse shapes and structures observed in exponentially growing cells under normal growth conditions (Floc’h et al, 2019). Nucleoid remodelling, and in particular nucleoid compaction, has been reported to occur in numerous bacteria, including human pathogens; it is one of the most rapid and effective adaptation strategies, particularly in response to sudden stress, and is often associated with major changes in gene expression. Transcriptomic studies of D. radiodurans have revealed that exposure to ionizing radiation leads to the up-regulation of many genes, including the Ddr (DNA Damage Response) genes A, B, C and D, a set of Deinococcus-specific genes encoding DNA-binding proteins that could potentially be involved in stress-induced nucleoid compaction.
In this work, we have used an integrated structural biology approach, combining protein crystallography with biochemical and biophysical assays, atomic force microscopy and molecular dynamic simulations, to decipher the structure and function of the DdrC protein. We notably determined its crystal structure and revealed that it folds as an unusual, asymmetric domain-swapped dimer. The asymmetry of this homo-dimer is remarkable in that it provides two distinct DNA binding surfaces, which allow DdrC to interact with two DNA duplexes and maintain circular DNA in a more constrained, negatively supercoiled conformation. DdrC acts like double sided tape! These findings led us to propose that DdrC may be a DNA-damage induced NAP that is rapidly recruited to the nucleoid following irradiation, where it can contribute to enhanced DNA packaging and limit the dispersion of DNA ends resulting from double strand breaks.
Banneville AS, Bouthier de la Tour C, De Bonis S, Hognon C, Colletier JP, Teulon JM, Le Roy A, Pellequer JL, Monari A, Dehez F, Confalonieri F, Servant P & Timmins J. Structural and functional characterization of DdrC, a novel DNA damage-induced nucleoid associated protein involved in DNA compaction. Nucleic Acids Research (2022) 50 (13) p. 7680-7696. DOI: 10.1093/nar/gkac563