denV gene of bacteriophage T4 restores DNA excision repair to mei-9 and mus201 mutants of Drosophila melanogaster.

Banga, Satnam S.; Boyd, James B.; Valerie, Kristoffer; Harris, Paul V.; Kurz, Eva; Riel, J K de

doi:10.1073/pnas.86.9.3227

Cited by 8 publications

(4 citation statements)

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“…Nucleic acid mutations which result from absorption of UV wavelengths can however be overcome by some bacteriophages, including phage T4, which have been found to carry their own repair genes, including denV for DNA excision repair 28 - 30 . With regards to the present study, further evaluation of the survivors of the 405 nm light-exposed phage population was out-with the scope of the study, however PDI and 405 nm light inactivation of viruses is thought to be due to Type I and Type II photoreactions, resulting in non-specific oxidative damage to structures such as the capsid, 31 therefore the potential for resistance development in exposed viruses, or other microorganisms, is unlikely 20 , 32 .…”

Section: Resultsmentioning

confidence: 99%

Inactivation ofStreptomycesphage ɸC31 by 405 nm light

et al. 2014

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Exposure to narrowband violet-blue light around 405 nm wavelength can induce lethal oxidative damage to bacteria and fungi, however effects on viruses are unknown. As photosensitive porphyrin molecules are involved in the microbicidal inactivation mechanism, and since porphyrins are absent in viruses, then any damaging effects of 405 nm light on viruses might appear unlikely. This study used the bacteriophage ɸC31, as a surrogate for non-enveloped double-stranded DNA viruses, to establish whether 405 nm light can induce virucidal effects. Exposure of ɸC31 suspended in minimal media, nutrient-rich media, and porphyrin solution, demonstrated differing sensitivity of the phage. Significant reductions in phage titer occurred when exposed in nutrient-rich media, with ~3-, 5- and 7-log10 reductions achieved after exposure to doses of 0.3, 0.5 and 1.4 kJ/cm2, respectively. When suspended in minimal media a 0.3-log10 reduction (P = 0.012) occurred after exposure to 306 J/cm2: much lower than the 2.7- and > 2.5-log10 reductions achieved with the same dose in nutrient-rich, and porphyrin-supplemented media, suggesting inactivation is accelerated by the photo-activation of light-sensitive components in the media. This study provides the first evidence of the interaction of narrowband 405 nm light with viruses, and demonstrates that viral susceptibility to 405 nm light can be significantly enhanced by involvement of exogenous photosensitive components. The reduced susceptibility of viruses in minimal media, compared with that of other microorganisms, provides further evidence that the antimicrobial action of 405 nm light is predominantly due to the photo-excitation of endogenous photosensitive molecules such as porphyrins within susceptible microorganisms.

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Section: Resultsmentioning

confidence: 99%

Inactivation ofStreptomycesphage ɸC31 by 405 nm light

et al. 2014

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“…Thus, certain prokaryotic DNA repair genes can function in eukaryotic cells (1,14,34). Indeed, we recently demonstrated that expression of the E. coli alkB gene in human cells confers the same alkylation-resistant phenotype as it does in E. coli, i.e., resistance to the S N 2, but not S N 1, alkylating agent (6).…”

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confidence: 99%

Suppression of Escherichia coli alkB mutants by Saccharomyces cerevisiae genes

1995

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The alkB gene is one of a group of alkylation-inducible genes in Escherichia coli, and its product protects cells from S N 2-type alkylating agents such as methyl methanesulfonate (MMS). However, the precise biochemical function of the AlkB protein remains unknown. Here, we describe the cloning, sequencing, and characterization of three Saccharomyces cerevisiae genes (YFW1, YFW12, and YFW16) that functionally complement E. coli alkB mutant cells. DNA sequence analysis showed that none of the three gene products have any amino acid sequence homology with the AlkB protein. The YFW1 and YFW12 proteins are highly serine and threonine rich, and YFW1 contains a stretch of 28 hydrophobic residues, indicating that it may be a membrane protein. The YFW16 gene turned out to be allelic with the S. cerevisiae STE11 gene. STE11 is a protein kinase known to be involved in pheromone signal transduction in S. cerevisiae; however, the kinase activity is not required for MMS resistance because mutant STE11 proteins lacking kinase activity could still complement E. coli alkB mutants. Despite the fact that YFW1, YFW12, and YFW16/STE11 each confer substantial MMS resistance upon E. coli alkB cells, S. cerevisiae null mutants for each gene were not MMS sensitive. Whether these three genes provide alkylation resistance in E. coli via an alkB-like mechanism remains to be determined, but protection appears to be specific for AlkB-deficient E. coli because none of the genes protect other alkylation-sensitive E. coli strains from killing by MMS.Various environmental compounds and intermediary metabolites contribute to DNA damage which, if left unrepaired, can be lethal or mutagenic. When DNA is exposed to alkylating agents such as methyl methanesulfonate (MMS) and Nmethyl-NЈ-nitro-N-nitrosoguanidine, more than a dozen different DNA adducts can be formed (37). Some adducts are harmless, but others cause mutations and cell death (37). Escherichia coli constitutively expresses at least two proteins, the Ogt O 6 -methylguanine/O 4 -methylthymine DNA methyltransferase (28) and the Tag 3-methyladenine (3MeA)/3-methylguanine DNA glycosylase (4,30), that specifically repair alkylated DNA lesions. In addition, four genes are induced as part of the adaptive response upon exposure to sublethal levels of an alkylating agent. These are the ada, alkB, alkA, and aidB genes, and their products protect cells against killing and mutation induced by further alkylation damage (22,32,36,40). The ada gene encodes another DNA repair methyltransferase, which transfers the methyl group from either O The E. coli alkB gene lies downstream from, and forms an operon with, the ada gene. The alkB gene is therefore coordinately regulated with the ada gene as part of the adaptive response to alkylating agents (22). E. coli alkB null mutants become extremely sensitive to killing induced by MMS, an S N 2 alkylating agent, marking the alkB pathway as an extremely effective defense mechanism against alkylation toxicity. The fact that MMS-treated phage survives better in wild...

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“…The Ada MTase also transfers methyl groups from methylphosphotriester DNA lesions to a second active-site cysteine residue, whereupon the Ada protein is transformed into an efficient transcriptional activator for the ada, alkA4, alkB, and aidB genes (19,34,38 Three prokaryotic DNA repair genes were previously introduced into mammalian cells, and their expression confers resistance to DNA-damaging agents. These are the T4 UV endonuclease (denV) gene (2,35,36), which provides UV resistance, and the E. coli ada (3,5,11,14,28) and ogt (9,39) genes, which provide alkylation resistance. Notably, DenV, 6255 on May 11, 2018 by guest…”

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confidence: 99%

“…These are the T4 UV endonuclease (denV) gene (2,35,36), which provides UV resistance, and the E. coli ada (3,5,11,14,28) and ogt (9,39) genes, which provide alkylation resistance. Notably, DenV, MTase) were gifts from R. B. Setlow, Brookhaven National Laboratories.…”

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confidence: 99%

The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity

1994

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Escherichia coli can ameliorate the toxic effects of alkylating agents either by preventing DNA alkylation or by repairing DNA alkylation damage. The alkylation-sensitive phenotype ofE. coli alkB mutants marks the alkB pathway as an extremely effective defense mechanism against the cytotoxic effects of the SN2, but not the SN1, alkylating agents. Although it is clear that AlkB helps cells to better handle alkylated DNA, no DNA alkylation repair function could be assigned to the purified AlkB protein, suggesting that AlkB either acts as part of a complex or acts to regulate the expression of other genes whose products are directly responsible for alkylation resistance. However, here we present evidence that the provision of alkylation resistance is an intrinsic function of the AlkB protein per se. We expressed the E. coli AlkB protein in two human cell lines and found that it confers the same characteristic alkylation-resistant phenotype in this foreign environment as it does in E. coli. AlkB expression rendered human cells extremely resistant to cell killing by the SN2 but not the SN1 alkylating agents but did not affect the ability of dimethyl sulfate (an SN2 agent) to alkylate the genome. We infer that SN2 agents produce a class of DNA damage that is not efficiently produced by SN1 agents and that AlkB somehow prevents this damage from killing the cell.The alkylation of DNA nitrogens and oxygens causes cell death and mutation in Eschenchia coli and in every cell type studied to date (8,19). The commonly studied alkylating agents, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methylnitrosourea (MNU), methyl methanesulfonate (MMS), and dimethyl sulfate (DMS), all produce the same collection of a dozen different alkylated lesions in DNA (32). However, because these agents alkylate DNA via different mechanisms, they produce the lesions in different proportions (18). MMS and DMS react via a SN2 mechanism and alkylate predominantly at DNA base nitrogens, producing very little alkylation at the oxygens in DNA bases and the oxygens in the sugarphosphate backbone. In contrast, MNNG and MNU react via an SN1 mechanism and efficiently alkylate both nitrogens and oxygens in DNA (7, 32).E. coli has several pathways that specifically ameliorate the toxic and mutagenic effects of DNA alkylation damage, and the absence of these pathways renders cells specifically sensitive to alkylating agents. Two DNA methyltransferases (MTases) encoded by the ada and ogt genes transfer methyl groups from various oxygens in DNA to an active-site cysteine residue in each of the MTase proteins. The Ada and Ogt MTases transfer methyl groups from 06-methylguanine (O6MeG) and 04-methylthymine (O4MeT); since O6MeG and O4MeT mispair during DNA replication, their repair protects E. coli from alkylation-induced mutation (19,25). The Ada MTase also transfers methyl groups from methylphosphotriester DNA lesions to a second active-site cysteine residue, whereupon the Ada protein is transformed into an efficient transcriptional activator for the ada, alkA4...

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denV gene of bacteriophage T4 restores DNA excision repair to mei-9 and mus201 mutants of Drosophila melanogaster.

Cited by 8 publications

References 27 publications

Inactivation ofStreptomycesphage ɸC31 by 405 nm light

Inactivation ofStreptomycesphage ɸC31 by 405 nm light

Suppression of Escherichia coli alkB mutants by Saccharomyces cerevisiae genes

The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity

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