The DNA excision repair system of the highly radioresistant bacterium <i>Deinococcus radiodurans</i> is facilitated by the pentose phosphate pathway

Zhang, Y.-M.; Liu, J.-K.; Wong, Tit-Yee

doi:10.1046/j.1365-2958.2003.03486.x

Cited by 35 publications

(23 citation statements)

References 37 publications

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“…The pentose phosphate could provide the cell with NADPH for detoxification of Fe-catalyzed synthesis of ROIs and synthesis of nucleotides for excision repair, while RitR could contribute to a reduction in Fe-catalyzed ROI synthesis by reducing iron uptake during exponential growth under high-iron conditions. In support of this interpretation, the resistance of Deinococcus radiodurans to UV light and H 2 O 2 was shown by Zhang et al to depend on an intact pentose phosphate pathway (59). In a comparison of a zwf ϩ (Zwischenferment, glucose-6-phosphate dehydrogenase) strain and a ⌬zwf strain of D. radiodurans, Zhang et al noted 1-order-of-magnitude reduced survival of the ⌬zwf mutant in 0.03% (10 mM) H 2 O 2 .…”

Section: Discussionmentioning

confidence: 66%

“…4). Given this observation, elevated expression of gnd-ritR would be expected to repress iron uptake while stimulating expression of the pentose phosphate pathway, which is responsible for (i) generating NADPH, which provides reducing power for detoxification of reactive oxygen intermediates, and (ii) synthesizing nucleotides needed for repair of Fe-catalyzed damage of DNA (46,59).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of Iron Transport inStreptococcus pneumoniaeby RitR, an Orphan Response Regulator

Ulijasz¹,

Andes

Glasner³

et al. 2004

J Bacteriol

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RitR (formerly RR489) is an orphan two-component signal transduction response regulator in Streptococcus pneumoniae that has been shown to be required for lung pathogenicity. In the present study, by using the rough strain R800, inactivation of the orphan response regulator gene ritR by allele replacement reduced pathogenicity in a cyclophosphamide-treated mouse lung model but not in a thigh model, suggesting a role for RitR in regulation of tissue-specific virulence factors. Analysis of changes in genome-wide transcript mRNA levels associated with the inactivation of ritR compared to wild-type cells was performed by the use of high-density DNA microarrays. Genes with a change in transcript abundance associated with inactivation of ritR included piuB, encoding an Fe permease subunit, and piuA, encoding an Fe carrier-binding protein. In addition, a dpr ortholog, encoding an H 2 O 2 resistance protein that has been shown to reduce synthesis of reactive oxygen intermediates, was activated in the wild-type (ritR ؉ ) strain. Microarray experiments suggested that RitR represses Fe uptake in vitro by negatively regulating the Piu hemin-iron transport system. Footprinting experiments confirmed site-specific DNA-binding activity for RitR and identified three binding sites that partly overlap the ؉1 site for transcription initiation upstream of piuB. Transcripts belonging to other gene categories found to be differentially expressed in our array studies include those associated with (i) H 2 O 2 resistance, (ii) repair of DNA damage, (iii) sugar transport and capsule biosynthesis, and (iv) two-component signal transduction elements. These observations suggest that RitR is an important response regulator whose primary role is to maintain iron homeostasis in S. pneumoniae. The name ritR (repressor of iron transport) for the orphan response regulator gene, rr489, is proposed.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Regulation of Iron Transport inStreptococcus pneumoniaeby RitR, an Orphan Response Regulator

Ulijasz¹,

Andes

Glasner³

et al. 2004

J Bacteriol

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“…The PPP is highly active in D. radiodurans (502), with the activity of glucose-6-phosphate dehydrogenase (G6PDH) (the marker enzyme for PPP) being 4-fold higher than that in Escherichia coli (683). G6PDH is upregulated in gamma-irradiated cells (677), and mutants defective in G6PDH are sensitive to UV light, hydrogen peroxide (H 2 O 2 ), and MMC (367,682). This pathway is employed for metabolizing glucose in TGY-grown cells into ribose-5-phosphate, glyceraldehyde-3-phosphate, and NADPH, which are all precursors for dNTPs (Fig.…”

Section: Vol 75 2011mentioning

confidence: 99%

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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“…This is because NADPH and ribose-5-phosphate that are intermediate metabolites of the alternative pentose phosphate pathway instigated by an increased FBPase-2 (or TIGAR) activity are important precursors of DNA biosynthesis and repair. 99 Despite acting as an antiapoptotic protein, with the inhibition of glycolysis TIGAR might be also involved in the tumor suppressive functions of p53 100 as cancer cells preferentially utilize glycolytic pathways for energy generation while downregulating their aerobic respiratory activity.…”

Section: P53 and The Oxidative Stress Responsementioning

confidence: 99%

The dark side of a tumor suppressor: anti-apoptotic p53

2008

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Depending on multiple factors DNA damage leads either to cell cycle arrest or apoptosis. One of the main players deciding the fate of a cell is the tumor suppressor p53 that modulates these responses in a transcription-dependent and -independent manner. Over the past few years, however, strong evidence accumulated that p53 engages also powerful pro-survival pathways by transcriptionally activating a multitude of genes whose products efficiently counteract apoptosis. Our review summarizes the current knowledge concerning approximately forty p53-regulated proteins that exert their anti-apoptotic potential by interfering with diverse cellular processes. These activities are surely essential for normal development and maintenance of a healthy organism, but may easily turn into the dark side of the tumor suppressor p53 contributing to tumorigenesis.

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The DNA excision repair system of the highly radioresistant bacterium Deinococcus radiodurans is facilitated by the pentose phosphate pathway

Abstract: SummaryDeinococcus radiodurans is highly resistant to radiation and mutagenic chemicals. Mutants defective in the putative glucose-6-phosphate dehydrogenase gene ( zwf

Cited by 35 publications

References 37 publications

Regulation of Iron Transport inStreptococcus pneumoniaeby RitR, an Orphan Response Regulator

Regulation of Iron Transport inStreptococcus pneumoniaeby RitR, an Orphan Response Regulator

Oxidative Stress Resistance inDeinococcus radiodurans

The dark side of a tumor suppressor: anti-apoptotic p53

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