The essential histone‐like protein HU plays a major role in <i>Deinococcus radiodurans</i> nucleoid compaction

Nguyen, Hong Ha; Tour, Claire Bouthier de la; Maga, Giovanni; Vannier, Françoise; Sommer, Suzanne; Servant, Pascale

doi:10.1111/j.1365-2958.2009.06766.x

Cited by 74 publications

(81 citation statements)

References 53 publications

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“…For example, deletion of HU from the E. coli genome is not lethal unless IHF and H-NS are deleted as well (31). In contrast, the disruption of HU is lethal for organisms in which it is the only NAP available (23,32,33). For H. pylori, we can easily obtain hup mutant strains which show normal growth at the exponential growth phase in vitro (15).…”

Section: Discussionmentioning

confidence: 99%

A Novel DNA-Binding Protein Plays an Important Role in Helicobacter pylori Stress Tolerance and Survival in the Host

Wang

Maier

2015

J Bacteriol

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The gastric pathogen Helicobacter pylori must combat chronic acid and oxidative stress. It does so via many mechanisms, including macromolecule repair and gene regulation. Mitomycin C-sensitive clones from a transposon mutagenesis library were screened. One sensitive strain contained the insertion element at the locus of hp119, a hypothetical gene. No homologous gene exists in any (non-H. pylori) organism. Nevertheless, the predicted protein has some features characteristic of histone-like proteins, and we showed that purified HP119 protein is a DNA-binding protein. A ⌬hp119 strain was markedly more sensitive (viability loss) to acid or to air exposure, and these phenotypes were restored to wild-type (WT) attributes upon complementation of the mutant with the wild-type version of hp119 at a separate chromosomal locus. The mutant strain was approximately10-fold more sensitive to macrophage-mediated killing than the parent or the complemented strain. Of 12 mice inoculated with the wild type, all contained H. pylori, whereas 5 of 12 mice contained the mutant strain; the mean colonization numbers were 158-fold less for the mutant strain. A proteomic (two-dimensional PAGE with mass spectrometric analysis) comparison between the ⌬hp119 mutant and the WT strain under oxidative stress conditions revealed a number of important antioxidant protein differences; SodB, Tpx, TrxR, and NapA, as well as the peptidoglycan deacetylase PgdA, were significantly less expressed in the ⌬hp119 mutant than in the WT strain. This study identified HP119 as a putative histone-like DNA-binding protein and showed that it plays an important role in Helicobacter pylori stress tolerance and survival in the host. Helicobacter pylori infects the stomachs of approximately 50% of humans and results in a series of human gastric diseases, including gastritis, peptic ulcers, and gastric cancer (1-4). The pathogenesis of H. pylori relies on its persistence in surviving a harsh environment, including acidity, peristalsis, and attack by phagocyte cells and their released reactive oxygen species (5). H. pylori survives on the surface of the stomach lining, often for the lifetime of its host, and causes a chronic inflammatory response. Under physiological conditions, H. pylori is thought to frequently suffer oxidative and acid stress (6, 7). H. pylori is equipped with diverse oxidant detoxification enzymes (e.g., superoxide dismutase, catalase, and peroxiredoxins) (8) and potent acid avoidance mechanisms (mainly urease) (9). To survive the harsh conditions, H. pylori regulates its gene expression in response to the stress signals; however, the bacterium lacks many response regulators known to occur in model microorganisms, such as the SOS response, OxyR/SoxR, and RpoS. Our current knowledge of the stress tolerance mechanisms cannot account for the well-described dynamic survival abilities of H. pylori.Studies in recent years have indicated that DNA recombination and repair play a significant role in H. pylori's persistent colonization of the host (10-14). ...

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Section: Discussionmentioning

confidence: 99%

A Novel DNA-Binding Protein Plays an Important Role in Helicobacter pylori Stress Tolerance and Survival in the Host

Wang

Maier

2015

J Bacteriol

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“…HU binds to four-way DNA junctions and may be additionally optimized for DNA recombination events by stabilizing recombination intermediates (208,209). Contrary to HU, one of the D. radiodurans Dps ("DNA protection during starvation") proteins, Dps1 (DR2263), was shown to promote DNA compaction in vitro (54) but not in vivo, as its depletion has no effect on genome condensation and cell viability (459). The D. radiodurans SMC ("structural maintenance of chromosomes") protein (DR1471), which is important for genome stabilization and DNA repair in eukaryotes (100, 365) and bacteria (640), has no role in genome condensation in D. radiodurans either (140a).…”

Section: Recombinational Processes In D Radiodurans Dna Repairmentioning

confidence: 99%

Section: Recombinational Processes In D Radiodurans Dna Repairmentioning

confidence: 99%

“…In vivo studies showed that the D. radiodurans HU ortholog (DRA0065) plays a major role in nucleoid organization and DNA compaction in D. radiodurans (459). It is essential for cell viability, as its progressive depletion leads to the decondensation of DNA, the fractionation of the nucleoid, and cell lysis (459). However, the nucleoid condensation role of HU is not supported by data from in vitro studies, which showed that HU cannot bend DNA or bind to DNA with nicks or gaps (209).…”

Section: Recombinational Processes In D Radiodurans Dna Repairmentioning

confidence: 99%

“…Editing of the pairing process by mismatch repair proteins is also expected to forestall recombination between nonhomologous fragments (373,490,510). Finally, tethering the ends of a given DSB to prevent them from dissociating via the cohesin-like RecN protein (518) or via genome condensation-promoting proteins, such as HU (459) and Dps1 (54) …”

Section: Fidelity Of Dna Repair In Irradiated D Radioduransmentioning

confidence: 99%

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Oxidative Stress Resistance inDeinococcus radiodurans

Slade

Radman

2011

Microbiol Mol Biol Rev

648

639

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SUMMARY Deinococcus radiodurans is a robust bacterium best known for its capacity to repair massive DNA damage efficiently and accurately. It is extremely resistant to many DNA-damaging agents, including ionizing radiation and UV radiation (100 to 295 nm), desiccation, and mitomycin C, which induce oxidative damage not only to DNA but also to all cellular macromolecules via the production of reactive oxygen species. The extreme resilience of D. radiodurans to oxidative stress is imparted synergistically by an efficient protection of proteins against oxidative stress and an efficient DNA repair mechanism, enhanced by functional redundancies in both systems. D. radiodurans assets for the prevention of and recovery from oxidative stress are extensively reviewed here. Radiation- and desiccation-resistant bacteria such as D. radiodurans have substantially lower protein oxidation levels than do sensitive bacteria but have similar yields of DNA double-strand breaks. These findings challenge the concept of DNA as the primary target of radiation toxicity while advancing protein damage, and the protection of proteins against oxidative damage, as a new paradigm of radiation toxicity and survival. The protection of DNA repair and other proteins against oxidative damage is imparted by enzymatic and nonenzymatic antioxidant defense systems dominated by divalent manganese complexes. Given that oxidative stress caused by the accumulation of reactive oxygen species is associated with aging and cancer, a comprehensive outlook on D. radiodurans strategies of combating oxidative stress may open new avenues for antiaging and anticancer treatments. The study of the antioxidation protection in D. radiodurans is therefore of considerable potential interest for medicine and public health.

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Comparative proteomics reveals key proteins recruited at the nucleoid of Deinococcus after irradiation‐induced DNA damage

et al. 2013

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The nucleoids of radiation-resistant Deinococcus species show a high degree of compaction maintained after ionizing irradiation. We identified proteins recruited after irradiation in nucleoids of Deinococcus radiodurans and Deinococcus deserti by means of comparative proteomics. Proteins in nucleoid-enriched fractions from unirradiated and irradiated Deinococcus were identified and semiquantified by shotgun proteomics. The ssDNA-binding protein SSB, DNA gyrase subunits GyrA and GyrB, DNA topoisomerase I, RecA recombinase, UvrA excinuclease, RecQ helicase, DdrA, DdrB, and DdrD proteins were found in significantly higher amounts in irradiated nucleoids of both Deinococcus species. We observed, by immunofluorescence microscopy, the subcellular localization of these proteins in D. radiodurans, showing for the first time the recruitment of the DdrD protein into the D. radiodurans nucleoid. We specifically followed the kinetics of recruitment of RecA, DdrA, and DdrD to the nucleoid after irradiation. Remarkably, RecA proteins formed irregular filament-like structures 1 h after irradiation, before being redistributed throughout the cells by 3 h post-irradiation. Comparable dynamics of DdrD localization were observed, suggesting a possible functional interaction between RecA and DdrD. Several proteins involved in nucleotide synthesis were also seen in higher quantities in the nucleoids of irradiated cells, indicative of the existence of a mechanism for orchestrating the presence of proteins involved in DNA metabolism in nucleoids in response to massive DNA damage. All MS data have been deposited in the ProteomeXchange with identifier PXD00196 (http://proteomecentral.proteomexchange.org/dataset/PXD000196).

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The essential histone‐like protein HU plays a major role in Deinococcus radiodurans nucleoid compaction

Cited by 74 publications

References 53 publications

A Novel DNA-Binding Protein Plays an Important Role in Helicobacter pylori Stress Tolerance and Survival in the Host

A Novel DNA-Binding Protein Plays an Important Role in Helicobacter pylori Stress Tolerance and Survival in the Host

Oxidative Stress Resistance inDeinococcus radiodurans

Comparative proteomics reveals key proteins recruited at the nucleoid of Deinococcus after irradiation‐induced DNA damage

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