title: DdrO is an essential protein that regulates the radiation desiccation response and the apoptotic-like cell death in the radioresistant Deinococcus radiodurans bacterium.
abstract: Deinococcus radiodurans is known for its extreme radioresistance. Comparative genomics identified a radiation-desiccation response (RDR) regulon comprising genes that are highly induced after DNA damage and containing a conserved motif (RDRM) upstream of their coding region. We demonstrated that the RDRM sequence is involved in cis-regulation of the RDR gene ddrB in vivo. Using a transposon mutagenesis approach, we showed that, in addition to ddrO encoding a predicted RDR repressor and irrE encoding a positive regulator recently shown to cleave DdrO in Deinococcus deserti, two genes encoding α-keto-glutarate dehydrogenase subunits are involved in ddrB regulation. In wild-type cells, the DdrO cell concentration decreased transiently in an IrrE-dependent manner at early times after irradiation. Using a conditional gene inactivation system, we showed that DdrO depletion enhanced expression of three RDR proteins, consistent with the hypothesis that DdrO acts as a repressor of the RDR regulon. DdrO-depleted cells loose viability and showed morphological changes evocative of an apoptotic-like response, including membrane blebbing, defects in cell division and DNA fragmentation. We propose that DNA repair and apoptotic-like death might be two responses mediated by the same regulators, IrrE and DdrO, but differently activated depending on the persistence of IrrE-dependent DdrO cleavage.
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Bâtiment 409, 91405, Orsay, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Devigne
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Bâtiment 409, 91405, Orsay, France.
authors.forename: Solenne
authors.initials: S
authors.lastname: Ithurbide
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Bâtiment 409, 91405, Orsay, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bouthier de la Tour
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Bâtiment 409, 91405, Orsay, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Passot
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Bâtiment 409, 91405, Orsay, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Mathieu
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Bâtiment 409, 91405, Orsay, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Sommer
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Bâtiment 409, 91405, Orsay, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Servant
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D003681:Dehydration; D034301:Deinococcus / Q000235:genetics* / Q000254:growth & development / Q000528:radiation effects* / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial; D023281:Genomics; D007655:Ketoglutarate Dehydrogenase Complex / Q000235:genetics; D016296:Mutagenesis; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D018085:Regulon
chemical_list: D001426:Bacterial Proteins; D007655:Ketoglutarate Dehydrogenase Complex