<scp>DdrO</scp> is an essential protein that regulates the radiation desiccation response and the apoptotic‐like cell death in the radioresistant <scp><i>D</i></scp><i>einococcus radiodurans</i> bacterium

Devigne, Alice; Ithurbide, Solenne; Tour, Claire Bouthier de la; Passot, Fanny; Mathieu, Martine; Sommer, Suzanne; Servant, Pascale

doi:10.1111/mmi.12991

Cited by 55 publications

(90 citation statements)

References 45 publications

(81 reference statements)

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“…While the IrrE‐mediated cleavage of DdrO was shown in solution after mixing the purified proteins and when coexpressed in Escherichia coli , the in vivo IrrE‐dependent DdrO cleavage in Deinococcus was observed only after exposure to radiation, in agreement with the radiation‐induced derepression of the RDR regulon. More recently, essentially the same conclusion for the role of IrrE in DdrO cleavage and gene induction was reached in two independent studies on D. radiodurans (Devigne et al., ; Wang et al., ). Additional results have been claimed for IrrE of D. radiodurans , namely that it binds, like DdrO, to the promoter regions of RDR genes (Lu, Chen, Xu, Shah, & Hua, ; Wang et al., ), although other studies indicated that IrrE does not bind DNA (Ohba, Satoh, Yanagisawa, & Narumi, ; Vujicic‐Zagar et al., ), and that the protease activity of apo‐IrrE could be restored by manganese but, remarkably, not by zinc ions (Wang et al., ).…”

Section: Introductionsupporting

confidence: 59%

“…Indeed, overexpression of IrrE and DdrO in E. coli showed cleavage of DdrO without applying a stress condition (Ludanyi et al., ). Moreover, a transposon insertion upstream of irrE in D. radiodurans resulted in increased expression of genes of the RDR regulon, probably because of enhanced expression of irrE caused by the transposon (Devigne et al., ).…”

Section: Resultsmentioning

confidence: 99%

“…Several years ago, three components were shown or predicted to have an important role in radiation‐ or desiccation‐induced gene expression in D. radiodurans , D. geothermalis , and D. deserti , namely the IrrE and DdrO proteins and the 17‐bp palindromic DNA motif called RDRM present at a variable position upstream of several induced genes, which suggested the presence of a conserved radiation/desiccation response (RDR) regulon (de Groot et al., ; Earl et al., ; Hua et al., ; Makarova et al., ; Vujicic‐Zagar et al., ). A link between these three components was demonstrated recently: DdrO functions as a repressor by binding to the RDRM that appeared to be located in or very close to the promoter of the radiation‐induced genes, including ddrO itself, and the constitutively expressed low‐abundance protein IrrE is a metalloprotease required for proteolytic inactivation of DdrO to derepress the genes, a process that is somehow stimulated after exposure of Deinococcus to radiation (de Groot et al., ; Devigne et al., ; Ludanyi et al., ; Wang et al., ). The IrrE‐dependent cleavage of DdrO, and thus the upregulated expression of RDR regulon genes, is essential for radiation tolerance.…”

Section: Discussionmentioning

confidence: 99%

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Conservation and diversity of the IrrE/DdrO‐controlled radiation response in radiation‐resistant Deinococcus bacteria

et al. 2017

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The extreme radiation resistance of Deinococcus bacteria requires the radiation‐stimulated cleavage of protein DdrO by a specific metalloprotease called IrrE. DdrO is the repressor of a predicted radiation/desiccation response (RDR) regulon, composed of radiation‐induced genes having a conserved DNA motif (RDRM) in their promoter regions. Here, we showed that addition of zinc ions to purified apo‐IrrE, and short exposure of Deinococcus cells to zinc ions, resulted in cleavage of DdrO in vitro and in vivo, respectively. Binding of IrrE to RDRM‐containing DNA or interaction of IrrE with DNA‐bound DdrO was not observed. The data are in line with IrrE being a zinc peptidase, and indicate that increased zinc availability, caused by oxidative stress, triggers the in vivo cleavage of DdrO unbound to DNA. Transcriptomics and proteomics of Deinococcus deserti confirmed the IrrE‐dependent regulation of predicted RDR regulon genes and also revealed additional members of this regulon. Comparative analysis showed that the RDR regulon is largely well conserved in Deinococcus species, but also showed diversity in the regulon composition. Notably, several RDR genes with an important role in radiation resistance in Deinococcus radiodurans, for example pprA, are not conserved in some other radiation‐resistant Deinococcus species.

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Section: Introductionsupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Conservation and diversity of the IrrE/DdrO‐controlled radiation response in radiation‐resistant Deinococcus bacteria

et al. 2017

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“…Two proteins, DdrO and IrrE, ensure the regulation of the RDR genes after DNA damage. DdrO is a negative transcriptional regulator that binds the RDRM sequence and represses the expression of the RDR genes [23–25]. IrrE is a metalloprotease [26] that cleaves, and thus inactivates DdrO after irradiation, leading to the transcriptional induction of the genes of the RDR regulon [23,24].…”

Section: Introductionmentioning

confidence: 99%

In vivo and in vitro characterization of DdrC, a DNA damage response protein in Deinococcus radiodurans bacterium

et al. 2017

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The bacterium Deinococcus radiodurans possesses a set of Deinococcus-specific genes highly induced after DNA damage. Among them, ddrC (dr0003) was recently re-annotated, found to be in the inverse orientation and called A2G07_00380. Here, we report the first in vivo and in vitro characterization of the corrected DdrC protein to better understand its function in irradiated cells. In vivo, the ΔddrC null mutant is sensitive to high doses of UV radiation and the ddrC deletion significantly increases UV-sensitivity of ΔuvrA or ΔuvsE mutant strains. We show that the expression of the DdrC protein is induced after γ-irradiation and is under the control of the regulators, DdrO and IrrE. DdrC is rapidly recruited into the nucleoid of the irradiated cells. In vitro, we show that DdrC is able to bind single- and double-stranded DNA with a preference for the single-stranded DNA but without sequence or shape specificity and protects DNA from various nuclease attacks. DdrC also condenses DNA and promotes circularization of linear DNA. Finally, we show that the purified protein exhibits a DNA strand annealing activity. Altogether, our results suggest that DdrC is a new DNA binding protein with pleiotropic activities. It might maintain the damaged DNA fragments end to end, thus limiting their dispersion and extensive degradation after exposure to ionizing radiation. DdrC might also be an accessory protein that participates in a single strand annealing pathway whose importance in DNA repair becomes apparent when DNA is heavily damaged.

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“…PprA is produced after ionizing radiation exposure by induction via PprI-dependent posttranslational modification to DdrO of the transcriptional regulator by proteolysis (24)(25)(26). PprA can bind to double-stranded DNA and inhibit its degradation by E. coli exonuclease III (14).…”

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confidence: 99%

Extended structure of pleiotropic DNA repair‐promoting protein PprA from Deinococcus radiodurans

et al. 2018

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Pleiotropic protein promoting DNA repair A (PprA) is a key protein facilitating the extreme radiation resistance of Deinococcus radiodurans. PprA is a unique protein to the genus Deinococcus and exists as an oligomer ranging from a tetramer to an ∼100‐mer depending on protein concentrations. Here, the X‐ray crystal structure of PprA was determined to clarify how PprA confers radiation resistance. The tertiary structure of dimeric PprA was elucidated by using mutants obtained with random and site‐directed mutagenesis methods (W183R and A139R); these mutants have disabled DNA binding and polymerization functions. Because the mutant A139R and W183R proteins have dimeric assemblies with 2 different interfaces (Interfaces 1 and 2), the linear and oligomerized PprA model was constructed as a left‐handed face‐to‐face periodic screw structure. In addition, the linear structure in solution was confirmed by small‐angle scattering experiments. The site‐directed mutational analysis identified essential basic amino acids for DNA binding. These analytical data support the hypothesis that a complex assembly of PprA molecules, which are extended and have a screw structure, surrounds and stretches the DNA strand, acting as a novel guide to colocalize the DNA strands for efficient DNA repairs.—Adachi, M., Shimizu, R., Shibazaki, C., Satoh, K., Fujiwara, S., Arai, S., Narumi, I., Kuroki, R. Extended structure of pleiotropic DNA repair‐promoting protein PprA from Deinococcus radiodurans. FASEB J. 33, 3647–3658 (2019). http://www.fasebj.org

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DdrO is an essential protein that regulates the radiation desiccation response and the apoptotic‐like cell death in the radioresistant Deinococcus radiodurans bacterium

Cited by 55 publications

References 45 publications

Conservation and diversity of the IrrE/DdrO‐controlled radiation response in radiation‐resistant Deinococcus bacteria

Conservation and diversity of the IrrE/DdrO‐controlled radiation response in radiation‐resistant Deinococcus bacteria

In vivo and in vitro characterization of DdrC, a DNA damage response protein in Deinococcus radiodurans bacterium

Extended structure of pleiotropic DNA repair‐promoting protein PprA from Deinococcus radiodurans

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