The effect of eye colour pigments on the action spectrum of Drosophila

In vivo absorption spectra for Drosophila melanogaster eye colour pigment classes (drosopterins and ommatins) were constructed by subtracting the whole eye electroretinographic (ERG) spectral sensitivities of cn and bw respectively from the sensitivities of white-eyed strains. In situ microspectrophotometric (MSP) absorption spectra were also obtained. Both the ERG and MSP drosopterin spectra show a visible peak at 500 nm compared to the 480 nm peak of in vitro drosopterins. For the ommatins, the ERG absorption spectrum peaks at 450 nm while the MSP spectrum peaks at 400 and 525 nm. The ERG spectrum is similar to the in vitro absorption spectrum of xanthommatin while the MSP spectrum is similar to the in vitro absorption spectrum of reduced xanthommatin. The ERG absorption spectra for the drosopterins and the ommatins yield an accurate prediction of the effect of the combined pigments in wild-type eyes. Newly emerged and 7 day post-emergence bw flies show quantitatively similar pigment absorption effects while the drosopterins depress the sensitivity of newly emerged cn flies to a greater extent than that of cn flies 7 days after emergence.     

β-Hydroxy-α-ketobutyric acid in Drosophila melanogaster,with reference to biosynthesis of drosopterins

A substance designated as compound D, which reacts spontaneously with 7,8-dihydropterin to give drosopterins, is found in Drosophila melanogaster. The compound was partially purified from the extract of flies by column chromatography and identified as β-hydroxy-α-ketobutyric acid by analysis of its 2,4-dinitrophenylhydrazone, mass spectrometry and reactivity with 7,8-dihydropterin. A highly significant correlation (r = 0.969, p < 0.001) was found between the amounts of the compound and drosopterins in the eye-pigment mutants of Drosophila. Changes of the compound during development of flies were also closely related to those of drosopterins. Based on these observations, a role of the compound in biosynthesis of drosopterins has been discussed.     

Redox-Dependent Gene Regulation in Rhodobacter sphaeroides 2.4.1T: Effects on Dimethyl Sulfoxide Reductase (dor) Gene Expression

The ability of Rhodobacter sphaeroides 2.4.1^T to respire anaerobically with the alternative electron acceptor dimethyl sulfoxide (DMSO) or trimethylamine N-oxide (TMAO) is manifested by the molybdoenzyme DMSO reductase, which is encoded by genes of the dor locus. Previously, we have demonstrated that dor expression is regulated in response to lowered oxygen tensions and the presence of DMSO or TMAO in the growth medium. Several regulatory proteins have been identified as key players in this regulatory cascade: FnrL, DorS-DorR, and DorX-DorY. To further examine the role of redox potentiation in the regulation of dor expression, we measured DMSO reductase synthesis and β-galactosidase activity from dor::lacZ fusions in strains containing mutations in the redox-active proteins CcoP and RdxB, which have previously been implicated in the generation of a redox signal affecting photosynthesis gene expression. Unlike the wild-type strain, both mutants were able to synthesize DMSO reductase under strictly aerobic conditions, even in the absence of DMSO. When cells were grown photoheterotrophically, dorC::lacZ expression was stimulated by increasing light intensity in the CcoP mutant, whereas it is normally repressed in the wild-type strain under such conditions. Furthermore, the expression of genes encoding the DorS sensor kinase and DorR response regulator proteins was also affected by the ccoP mutation. By using CcoP-DorR and CcoP-DorY double mutants, it was shown that the DorR protein is strictly required for altered dor expression in CcoP mutants. These results further demonstrate a role for redox-generated responses in the expression of genes encoding DMSO reductase in R. sphaeroides and identify the DorS-DorR proteins as a redox-dependent regulatory system controlling dor expression.     

Germ line dependence of the deep orange maternal effect in Drosophila

Pole cell transplantations were used to determine the tissue specificity of maternal effects in Drosophila. The deep orange maternal effect is shown to be germ line autonomous. A cytoplasmic injection assay was used to determine when the dor⁺ substance could be detected in the developing oocyte. The dor⁺ substance is present during the early stages of vitellogenesis but could not be detected in the yolk of the embryo after blastoderm cellularization.     

Developmental changes of sepiapterin synthase activity associated with a variegated purple gene in Drosophila melanogaster

A variegated position effect on the autonomous gene, purple, has been studied enzymologically in Drosophila melanogaster. Sepiapterin synthase, the enzyme system associated with pr ⁺, was examined for activity in different developmental stages of the fly. The results indicate that T(Y:2) pr ^c5, cn/pr^c4 cn flies (flies in which pr ⁺ has been translocated and which exhibit variegation) have a reduced amount of enzyme activity as compared with both Oregon-R and pr ¹ flies. This reduction in activity was not found in larval stages, which suggests that the inactivation process probably occurs in late larval or early pupal stages. The phenotype of the variegated adult has white eyes with red-colored spots and patches where drosopterins occur. The phenotype of the fly carrying the translocation is modified by the presence of additional Y chromosomes. This extends the observation from other systems that extra heterochromatin acts to suppress the variegated position effect. The advantages of studying the variegation by measuring enzyme activity, as well as the phenotypic expression, are several; for example, the developmental time at which variegation occurs may be estimated even though drosopterin synthesis is not occurring.The Oak Ridge National Laboratory is operated by Union Carbide Corporation for the Department of Energy under Contract No. W-7405-eng-26.     

NGF/PI3K signaling-mediated epigenetic regulation of delta opioid receptor gene expression

The G protein-coupled delta opioid receptor gene (dor) has been associated with neuronal survival, differentiation, and neuroprotection. Our previous study identified PI3K/Akt/NF-κB signaling is a main downstream signaling pathway in nerve growth factor (NGF)-induced temporal expression of the dor gene in the PC12 cell model. It is still unknown how NGF/PI3K signaling regulates the expression of the dor gene in the nucleus. In the current study, we investigated how PI3K signaling affected epigenetic modifications of histone H3 Lys⁹ (H3K9) in the 5′-UTR region of the rat dor gene locus. NGF treatment resulted in the global reversal of H3K9 trimethylation in cells. Moreover, the locus-specific reversal of H3K9 trimethylation and acetylation of H3K9 were dependent upon NGF/PI3K signaling and temporally well correlated with NGF-induced gene expression. These results indicate the importance of epigenetic modifications of H3K9, particularly the reversal of trimethylated H3K9, in the regulation of NGF/PI3K-dependent genes during neuronal differentiation.     

Colorimetric Measurement of Triglycerides Cannot Provide an Accurate Measure of Stored Fat Content in Drosophila

Drosophila melanogaster has recently emerged as a useful model system in which to study the genetic basis of regulation of fat storage. One of the most frequently used methods for evaluating the levels of stored fat (triglycerides) in flies is a coupled colorimetric assay available as a kit from several manufacturers. This is an aqueous-based enzymatic assay that is normally used for measurement of mammalian serum triglycerides, which are present in soluble lipoprotein complexes. In this short communication, we show that coupled colorimetric assay kits cannot accurately measure stored triglycerides in Drosophila. First, they fail to give accurate readings when tested on insoluble triglyceride mixtures with compositions like that of stored fat, or on fat extracted from flies with organic solvents. This is probably due to an inability of the lipase used in the kits to efficiently cleave off the glycerol head group from fat molecules in insoluble samples. Second, the measured final products of the kits are quinoneimines, which absorb visible light in the same wavelength range as Drosophila eye pigments. Thus, when extracts from crushed flies are assayed, much of the measured signal is actually due to eye pigments. Finally, the lipoprotein lipases used in colorimetric assays also cleave non-fat glycerides. The glycerol backbones liberated from all classes of glycerides are measured through the remaining reactions in the assay. As a consequence, when these assay kits are used to evaluate tissue extracts, the observed signal actually represents the amount of free glycerols together with all types of glycerides. For these reasons, findings obtained through use of coupled colorimetric assays on Drosophila samples must be interpreted with caution. We also show here that using thin-layer chromatography to measure stored triglycerides in flies eliminates all of these problems.     

Biosynthesis of "drosopterins" by an enzyme system from Drosophila melanogaster.

The red eye pigment of Drosophila melanogaster consists of six complex pteridines known as neodrosopterin, drosopterin, isodrosopterin, fraction e, and aurodrosopterins (2); these pigments are greatly reduced in the purple mutant. Conditions for biosynthesis of these "drosopterins" are described and compared with those for the synthesis of sepiapterin. The enzymes are contained in a soluble, pteridine-free extract obtained between 40 and 60% saturated ammonium sulfate. The results indicate that sepiapterin synthase consists of two enzymes, the first of which provides a precursor for "drosopterin" biosynthesis. The evidence is (1) the purple mutant, low in accumulated sepiapterin and "drosopterins", is known to have approximately 10% of the sepiapterin synthase activity of wild type; (2) unlabeled sepiapterin does not cause isotope dilution of "drosopterin" synthesis; (3) the 600g pellet prepared from a wild-type head homogenate contains "drosopterin" synthesizing activity and no sepiapterin synthase, yet a heat-labile factor in this fraction stimulates sepiapterin synthesis in the 100000g supernatant of wild-type or pr flies; (4) sepiapterin and "drosopterin" syntheses require Mg2+; (5) sepiapterin synthesis is stimulated by NADPH; "drosopterin" synthesis responds to either NADPH or NADH. Although "drosopterins" are complex pteridine-type pigments, we have demonstrated their biosynthesis by soluble enzymes. This allows us to consider investigation into the mechanism by which the amounts of these pigments are regulated.     

Does a homogeneous population of elementary movement detectors activate the landing response of blowflies,Calliphora erythrocephala?

The landing response of tethered flying blowflies, Calliphora erythrocephala, was elicited by moving periodic gratings, and by stripes moving apart. The influence of binocular interactions on the landing response was investigated by comparing the responses of intact (“binocular”) animals to the response of flies which had one eye covered with black paint (“monocular” flies) effectively eliminating the input from this eye. Directions of motion eliciting a maximal response (preference direction) were determined in intact animals, and in “molecular” flies for different regions of the visual field. Preference directions determined in “monocular” flies follow the orientation of Z-axes (Fig. 4). Preference directions determined in intact animals and in “monocular” flies differ in the binocular eye region: in intact animals, the preference directions corresponds to vertical directions of motion; whereas the preference direction determined for the same area in “monocular” flies are inclined obliquely against the vertical plane. Sex-specific differences were found for the ventral binocular eye region in which the shift of preference directions is more pronounced in male than in female flies. The experimental data support the hypothesis that elementary movement detectors are aligned along the Z-axes of the eye, and that preference directions deviating from the orientation of elementary movement detectors are caused by binocular interactions.     

Parameters influencing the acquisition of competence for metamorphosis in imaginal disks of Drosophila

When imaginal disks from first and early second instar larvae of Drosophila are transplanted into larval hosts that are ready to pupate, they are unable to differentiate adult structures. The disks gradually become competent to respond with imaginal differentiation towards the end of the second larval instar (Fig. 1). The first sign of imaginal differentiation is a light-orange pigment that appears in the presumptive eye region when eye-antennal disks from early second instar larvae were subjected to immediate metamorphosis. This pigment was identified as being composed of ommochromes and drosopterins.Incompetent eye-antennal disks from early second instar donors were cultured in adult females for 2 to 5 days, and then retransplanted into late third instar larval hosts. If the adult host flies were kept on standard food the disks grew by cell multiplication (Fig. 2c) and became competent to undergo imaginal differentiation (Fig. 3). If, on the other hand, the adult hosts were starved on a protein-free sugar diet, cell divisions were effectively blocked in the disks. These did not noticeably grow (Fig. 2b) and remained incompetent (Fig. 3). The block caused by starvation proved to be reversible. Based on these results the hypothesis is advanced that the acquisition of competence requires a minimum number of cell divisions to take place in the disk primordium.     

p62 Plays a Protective Role in the Autophagic Degradation of Polyglutamine Protein Oligomers in Polyglutamine Disease Model Flies

Oligomer formation and accumulation of pathogenic proteins are key events in the pathomechanisms of many neurodegenerative diseases, such as Alzheimer disease, ALS, and the polyglutamine (polyQ) diseases. The autophagy-lysosome degradation system may have therapeutic potential against these diseases because it can degrade even large oligomers. Although p62/sequestosome 1 plays a physiological role in selective autophagy of ubiquitinated proteins, whether p62 recognizes and degrades pathogenic proteins in neurodegenerative diseases has remained unclear. In this study, to elucidate the role of p62 in such pathogenic conditions in vivo, we used Drosophila models of neurodegenerative diseases. We found that p62 predominantly co-localizes with cytoplasmic polyQ protein aggregates in the MJDtr-Q78 polyQ disease model flies. Loss of p62 function resulted in significant exacerbation of eye degeneration in these flies. Immunohistochemical analyses revealed enhanced accumulation of cytoplasmic aggregates by p62 knockdown in the MJDtr-Q78 flies, similarly to knockdown of autophagy-related genes (Atgs). Knockdown of both p62 and Atgs did not show any additive effects in the MJDtr-Q78 flies, implying that p62 function is mediated by autophagy. Biochemical analyses showed that loss of p62 function delays the degradation of the MJDtr-Q78 protein, especially its oligomeric species. We also found that loss of p62 function exacerbates eye degeneration in another polyQ disease fly model as well as in ALS model flies. We therefore conclude that p62 plays a protective role against polyQ-induced neurodegeneration, by the autophagic degradation of polyQ protein oligomers in vivo, indicating its therapeutic potential for the polyQ diseases and possibly for other neurodegenerative diseases.     

Uptake and incorporation in pteridines of externally supplied GTP in normal and pigment-deficient eyes ofDrosophila melanogaster

Some aspects of the synthesis of drosopterins in the eyes ofDrosophila melanogaster have been studied in flies with different levels ofwhite gene expression. The activity of GTP cyclohydrolase was found to differ between wild-type and yellow-eyed mutantsin vivo but notin vitro. To elucidate the uptake of substrate, we measured the removal of labeled GTP from the incubation medium by excised pupal eyes and followed the subsequent fate of this label. It was found that GTP was dephosphorylated to guanosine extracellularly before label was taken up by the eye tissue. The uptake was much lower in yellow and white eyes than in wild-type eyes, and in the latter, a considerable part of the label was present in pteridine compounds. The strain differences in the uptake of label seem to be due to different rates of intracellular utilization of guanine derivatives in pteridine synthesis. We suggest that this is caused by a hampered transport of precursor (possibly GTP) in white andzeste eyes through the membrane of red pigment granules.This project was sponsored by the Swedish Natural Science Research Council.     

Interspecies Interactions Determine the Impact of the Gut Microbiota on Nutrient Allocation in Drosophila melanogaster

The animal gut is perpetually exposed to microorganisms, and this microbiota affects development, nutrient allocation, and immune homeostasis. A major challenge is to understand the contribution of individual microbial species and interactions among species in shaping these microbe-dependent traits. Using the Drosophila melanogaster gut microbiota, we tested whether microbe-dependent performance and nutritional traits of Drosophila are functionally modular, i.e., whether the impact of each microbial taxon on host traits is independent of the presence of other microbial taxa. Gnotobiotic flies were constructed with one or a set of five of the Acetobacter and Lactobacillus species which dominate the gut microbiota of conventional flies (Drosophila with untreated microbiota). Axenic (microbiota-free) flies exhibited prolonged development time and elevated glucose and triglyceride contents. The low glucose content of conventional flies was recapitulated in gnotobiotic Drosophila flies colonized with any of the 5 bacterial taxa tested. In contrast, the development rates and triglyceride levels in monocolonized flies varied depending on the taxon present: Acetobacter species supported the largest reductions, while most Lactobacillus species had no effect. Only flies with both Acetobacter and Lactobacillus had triglyceride contents restored to the level in conventional flies. This could be attributed to two processes: Lactobacillus-mediated promotion of Acetobacter abundance in the fly and a significant negative correlation between fly triglyceride content and Acetobacter abundance. We conclude that the microbial basis of host traits varies in both specificity and modularity; microbe-mediated reduction in glucose is relatively nonspecific and modular, while triglyceride content is influenced by interactions among microbes.     

Relevant expression of Drosophila heme oxygenase is necessary for the normal development of insect tissues

Heme oxygenase (HO) is a rate-limiting step of heme degradation, which catalyzes the conversion of heme into biliverdin, iron, and CO. HO has been characterized in micro-organisms, insects, plants, and mammals. The mammalian enzyme participates in adaptive and protective responses to oxidative stress and various inflammatory stimuli. The present study reports the use of RNA-interference (RNAi) to suppress HO in the multicellular eukaryote Drosophila. Eye imaginal disc-specific suppression of the Drosophila HO homolog (dHO) conferred serious abnormal eye morphology in adults. Deficiency of the dHO protein resulted in increased levels of iron and heme in larvae. The accumulation of iron was also observed in the compound eyes of dHO-knockdown adult flies. In parallel with the decrease of dHO, the expression of δ-aminolevulinic acid synthase, the first enzyme of the heme-biosynthetic pathway, in larvae was decreased markedly, suggesting that heme biosynthesis was totally suppressed by dHO-deficiency. The activation of caspase-3 occurred in eye imaginal discs of dHO-knockdown flies, indicating the occurrence of apoptosis in the discs. On the other hand, the overexpression of dHO resulted in a weak but significant rough eye phenotype in adults. Taken together, considering that dHO is not a stress-inducible protein, the expression of dHO can be tightly regulated at developmental stages and the relevant expression is necessary for the normal development of tissues in Drosophila.     

Distribution of third-stage Dirofilaria roemeri (Nematoda: Filarioidea) in the tissues of tabanidae (Diptera)

The distribution of third-stage D. roemeri in its tabanid intermediate host was observed in histological sections of naturally infected Dasybasis oculata and Tabanus parvicallosus. Larvae invade the brain, eye, nerve cord, muscles of the mouthparts, horizontal and indirect flight muscles, fat body, hind gut and gonad of flies. Third-stage D. roemeri migrate from the abdomen via the haemocoelic spaces of the thorax to the head of the fly. Evidence suggests that larvae escape from the intermediate host by rupturing the tip of the labrum or the labro-epipharyngeal membranes. Injury was observed in the eye, nerve cord and musculature. There was no evidence that the parasite had a detrimental effect on the host and tabanids showed no response to the presence of filarioids. Species of Dasybasis and Tabanus acting as intermediate host of D. roemeri in nature epitomize the concept of a ‘good’ host.     

Guanine Deaminase Functions as Dihydropterin Deaminase in the Biosynthesis of Aurodrosopterin, a Minor Red Eye Pigment of Drosophila

Dihydropterin deaminase, which catalyzes the conversion of 7,8-dihydropterin to 7,8-dihydrolumazine, was purified 5850-fold to apparent homogeneity from Drosophila melanogaster. Its molecular mass was estimated to be 48 kDa by gel filtration and SDS-PAGE, indicating that it is a monomer under native conditions. The pI value, temperature, and optimal pH of the enzyme were 5.5, 40 °C, and 7.5, respectively. Interestingly the enzyme had much higher activity for guanine than for 7,8-dihydropterin. The specificity constant (k_cat/K_m) for guanine (8.6 × 10⁶ m⁻¹·s⁻¹) was 860-fold higher than that for 7,8-dihydropterin (1.0 × 10⁴ m⁻¹·s⁻¹). The structural gene of the enzyme was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis as CG18143, located at region 82A1 on chromosome 3R. The cloned and expressed CG18143 exhibited both 7,8-dihydropterin and guanine deaminase activities. Flies with mutations in CG18143, SUPor-P/Df(3R)A321R1 transheterozygotes, had severely decreased activities in both deaminases compared with the wild type. Among several red eye pigments, the level of aurodrosopterin was specifically decreased in the mutant, and the amount of xanthine and uric acid also decreased considerably to 76 and 59% of the amounts in the wild type, respectively. In conclusion, dihydropterin deaminase encoded by CG18143 plays a role in the biosynthesis of aurodrosopterin by providing one of its precursors, 7,8-dihydrolumazine, from 7,8-dihydropterin. Dihydropterin deaminase also functions as guanine deaminase, an important enzyme for purine metabolism.The complexity of the eye color phenotypes of the fruit fly Drosophila melanogaster has been the subject of numerous investigations for more than 90 years. Two classes of pigments contribute to the eye color of Drosophila: brown “ommochromes” and red “drosopterins.” Drosopterins, first reported by Lederer (1) and subsequently by Viscontini et al. (2), consist of at least five compounds, which have been referred to as drosopterin, isodrosopterin, neodrosopterin, aurodrosopterin, and “fraction e” (3). Among the red pigments, drosopterin and isodrosopterin are the major components, whereas aurodrosopterin and neodrosopterin are minor pigments in wild type flies.The chemical structure of drosopterin was determined by Pfleiderer and co-worker (4). Drosopterin and its enantiomer, isodrosopterin, consist of a pentacyclic ring system containing a 5,6,7,8-tetrahydropterin (=2-amino-5,6,7,8-tetrahydropteridin-4(1H)-one), a 2-amino-3,7,8,9-tetrahydro-4H-pyrimido[4,5-b][1,4]diazepin-4-one, and a pyrrole ring (Scheme 1). Based on ¹H NMR and UV/visible spectral analyses, the structure of aurodrosopterin was elucidated in 1993 by Yim et al. (5), who found that it is the same as that of drosopterin except that it has one less amino group in the pteridine portion. The presence or absence of an amino group in the pteridine moiety is the key characteristic that distinguishes drosopterin from aurodrosopterin (Scheme 1). They also reported the presence of isoaurodrosopterin based on thin layer chromatographic analyses of Drosophila head extracts using various solvent systems (5).Open in a separate windowSCHEME 1.Proposed pathway for the biosynthesis of drosopterins in D. melanogaster. The red eye pigments in Drosophila are collectively called drosopterins. Drosopterin (a major red eye pigment; labeled D) is produced nonenzymatically by the one-to-one condensation of 7,8-dihydropterin and PDA (10). Aurodrosopterin (a minor red eye pigment; labeled A), which has one less amino group in the pteridine portion of the structure, was shown to be produced nonenzymatically by the condensation of 7,8-dihydrolumazine and PDA (5).The first step leading to the biosynthesis of drosopterins is the formation of 7,8-dihydroneopterin triphosphate from GTP by GTP cyclohydrolase I, which is encoded by Punch (6). 7,8-Dihydroneopterin triphosphate is then converted to 6-pyruvoyl tetrahydropterin (6-PTP)³ by PTP synthase, the product of the purple gene (7–9). Next 6-PTP is converted to pyrimidodiazepine (PDA) by PDA synthase, which is a member of the Omega class glutathione S-transferases and is encoded by the sepia gene (10, 11). Aurodrosopterin and its enantiomer, isoaurodrosopterin, are produced nonenzymatically by the one-to-one condensation of 7,8-dihydrolumazine and PDA under acidic conditions (5) in a manner similar to the production of drosopterin and isodrosopterin, which are produced by a similar nonenzymatic condensation of 7,8-dihydropterin and PDA (Scheme 1).In the course of investigating the metabolic fate of tetrahydrobiopterin, Rembold and co-workers (12) found that tetrahydrobiopterin can be degraded to 6-hydroxylumazine by rat liver homogenates. They proposed that tetrahydrobiopterin was converted by nonenzymatic side chain release to 7,8-dihydropterin, which was converted to 7,8-dihydrolumazine, the deaminated counterpart of 7,8-dihydropterin, by a deaminase present in the crude extracts. 7,8-Dihydrolumazine is then converted to 7,8-dihydro-6-hydroxylumazine by xanthine oxidase and subsequently to 6-hydroxylumazine by autoxidation. This series of reactions was also observed in D. melanogaster. Takikawa et al. (13) demonstrated the conversion of 7,8-dihydropterin to 6-hydroxylumazine using partially purified fly extracts. However, the enzymatic properties of the deaminase and the identity of the gene encoding the protein have not yet been established.Here we purified and characterized Drosophila dihydropterin deaminase and identified its structural gene, CG18143, by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis. We provide clear evidence that CG18143, previously annotated as the guanine deaminase gene, is directly involved in the biosynthesis of aurodrosopterin, a minor red eye pigment in Drosophila.     

Cloning and Characterization of a Novel Drosophila Stress Induced DNase

Drosophila melanogaster flies mount an impressive immune response to a variety of pathogens with an efficient system comprised of both humoral and cellular responses. The fat body is the main producer of the anti-microbial peptides (AMPs) with anti-pathogen activity. During bacterial infection, an array of secreted peptidases, proteases and other enzymes are involved in the dissolution of debris generated by pathogen clearance. Although pathogen destruction should result in the release a large amount of nucleic acids, the mechanisms for its removal are still not known. In this report, we present the characterization of a nuclease gene that is induced not only by bacterial infection but also by oxidative stress. Expression of the identified protein has revealed that it encodes a potent nuclease that has been named Stress Induced DNase (SID). SID belongs to a family of evolutionarily conserved cation-dependent nucleases that degrade both single and double-stranded nucleic acids. Down-regulation of sid expression via RNA interference leads to significant reduction of fly viability after bacterial infection and oxidative stress. Our results indicate that SID protects flies from the toxic effects of excess DNA/RNA released by pathogen destruction and from oxidative damage.