In bacteria, genomic DNA compaction is governed by several mechanisms : DNA supercoiling, DNA compaction by nucleoid-associated proteins (NAPs) and several other factors, including cellular crowding and depletion forces. However, the molecular mechanisms underlying these processes are still only poorly understood.
To fill some these knowledge gaps, we have set out to study the nucleoid of the radiation resistant bacterium, Deinococcus radiodurans using an integrated approach combining in vitro, in silico and in vivo data. We notably demonstrated that the complex, multipartite genome of D. radiodurans is organised into a singularly more compact and surprisingly dynamic nucleoid compared to some radio-sensitive bacteria, such as E. coli. In D. radiodurans, the nucleoid adopts multiple distinct configurations as the bacterium progresses through its cell cycle. Such major nucleoid rearrangements have never been described before and clearly demonstrate that nucleoid organisation and cell cycle progression are closely linked.
By combining genetic, biochemical, structural biology and advanced imaging approaches, our objective is now to shed light on the molecular mechanisms at the origin of this remarkable nucleoid organisation and plasticity, and to determine how these mechanisms contribute to the exceptional radioresistance of D. radiodurans in response to extreme radiation (UV-C and gamma ray).
Collaborations
Dominique BOURGEOIS (PIXEL team, I2SR, IBS)
Pascale SERVANT & Fabrice CONFALONIERI (I2BC, Gif-sur-Yvette)
François DEHEZ (LPCT, Nancy)
Irina GUTSCHE (MICA Group, IBS)
Jean-Luc PELLEQUER (MEM Group, IBS)
Major publications
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.
Chen SW, Banneville A-S, Teulon J-M, Timmins J and Pellequer J-L. Nanoscale surface structures of DNA bound to Deinococcus radiodurans HU unveiled by atomic force microscopy. Nanoscale (2020) 12, 22628. DOI : 10.1039/D0NR05320A.
Hognon C, Garaude S, Timmins J, Chipot C, Dehez F and Monari A. Molecular basis of DNA packaging in bacteria revealed by all-atoms molecular dynamic simulations : The case of histone-like proteins in Borrelia burgdorferi. J. Phys. Chem. Lett. (2019) 10, 7200-7207. DOI : 10.1021/acs.jpclett.9b02978.
Floc’h K, Lacroix F, Servant P, Wong YS, Kleman JP, Bourgeois D and Timmins J. Cell morphology and nucleoid dynamics in dividing D. radiodurans. Nat Commun. (2019) 10 (1). p.3815. DOI : 10.1038/s41467-019-11725-5.
Floc’h K, Lacroix F, Barbieri L, Servant P, Galland R, Butler C, Sibarita JB, Bourgeois D and Timmins J. Bacterial cell wall nanoimaging by autoblinking microscopy. Scientific Reports (2018) 8 (1) p. 14038. DOI :