Biosciences and Biotechnology Institute of Aix-Marseille
Deinococcus bacteria, cocci or rods, present colored colonies on Petri dishes due to the presence of carotenoids. These bacteria tolerate much higher doses of ionizing radiation than most bacteria and human cells (no loss of survival at 5000 Gray (Gy) while a dose of 10 Gy is lethal to humans). This extreme resistance is due to the ability of
Deinococcus to reconstitute an intact genome from a genome fragmented by irradiation, including repair of many double-strand breaks that are lethal to most organisms (De Groot et al. (2009)
Their secret, discovered step by step in recent years, results from a combination of many factors and finely regulated repair and protection mechanisms (Lim, Jung, Blanchard, De Groot (2019)
FEMS Microbiol Rev). However, many mechanisms and functions of new proteins have still to be deciphered.Elucidating how Deinococci resist radiation may lead to a better understanding of radiation resistance of other organisms or cells (e.g. some cancer cells with increased resistance to radiotherapy), or conversely, to an understanding of why some cells are more radiosensitive than others.
After irradiation, gene expression leading to cell survival is induced via an original SOS-independent way. Two key proteins control this genetic "switch": the metallopeptidase IrrE and the repressor DdrO (Ludanyi et al. 2014; Blanchard et al. 2017), for which we have solved the 3D structure.
IrrE presents an unique combination of two domains: a metallopeptidase domain and a putative sensor domain (Vujicic-Zagar et al. 2009). DdrO consists of a classical HTH-type DNA binding domain and a C-terminal domain that is the target of IrrE and also shows a new fold (De Groot et al. 2019).
Under standard conditions, DdrO binds as a dimer to the two half-sites of a 17bp palindromic motif, therefore inhibiting transcription of the IrrE/DdrO dependent genes. After irradiation/desiccation, DdrO is cleaved by IrrE rapidly inducing the expression of DNA repair genes, genes of unknown function and
ddrO itself. Our collaborators at I2BC (Team of F. Confalonieri, Paris Saclay) discovered that the prolonged absence of DdrO induces apoptotic-like cell death in
Deinococcus (Devigne et al. 2015). The phenomenon of programmed cell death is poorly characterized in bacteria.
For more information on the radiation response molecular mechanism see the article De Groot et al (2019) and the associated
CNRS/INSB highlight.Further characterisation of this original mechanism is the subject of the ANR NOVOREP ANR-2019-CE12-0010 which started in January 2020.
Rémi Dulermo (2006-2009),
Monika Ludanyi (2011-2014), Romaric Magerand (2017-
Collaborators from BIAM, CEA CadaracheM. Siponen, P. Arnoux, D. Pignol (MEM), D. Lemaire (IPM), P. Rey (PPV)
Collaborators in France and in South KoreaF. Confalonieri, S. Sommer (I2BC, Institut de Biologie Intégrative de la Cellule, Univ. Paris Saclay, France)P. Roche (CRCM, Inserm, CNRS, Institut Paoli Calmettes, Aix Marseille Univ., France)J. Armengaud (CEA Marcoule, DRF/JOLIOT, France)
Genoscope (CEA Institut de génomique, Centre National de Séquençage, France)J.-H. Jung et S. Lim (KAERI, Korea Atomic Energy Research Institute, South Korea)
FEMS Microbiology Reviews 2019 : This meta-analysis was the subject of a
press release on October 18, 2018 via the CNRS and the CEA: Nature's unsuspected resources to resist radiation.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.