Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.30.2 (endonuclease)
18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human apurinic/apyrimidinic endonuclease activity, called AP endonuclease I, is missing from or altered specifically in cells cultured from Xeroderma pigmentosum group-D individuals (XP-D cells) (Kuhnlein, U., Lee, B., Penhoet, E. E., and Linn, S. (1978) Nucleic Acids Res. 5,951-960). We have now observed that another nuclease activity, UV endonuclease III, is similarly not detected in XP-D cells and is inseparable from the AP endonuclease I activity. This activity preferentially cleaves the phosphodiester backbone of heavily ultraviolet-irradiated DNA at unknown lesions as well as at one of the phosphodiester bonds within a cyclobutane pyrimidine dimer. The nuclease activities have been purified from mouse cells to yield a peptide of M(r) = 32,000, whose sequence indicates identity with ribosomal protein S3. The nuclease activities all cross-react with immunopurified antibody directed against authentic rat ribosomal protein S3, and, upon expression in Escherichia coli of a cloned rat cDNA for ribosomal protein S3, each of the activities was recovered and was indistinguishable from those of the mammalian UV endonuclease III. Moreover, the protein expressed in E. coli and its activities cross-react with the rat protein antibody. Ribosomal protein S3 contains a potential nuclear localization signal, and the protein isolated as a nuclease also has a glycosylation pattern consistent with a nuclear localization as determined by lectin binding. The unexpected role of a ribosomal protein in DNA damage processing and the unexplained inability to detect the nuclease activities in extracts from XP-D cells are discussed.
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PMID:Implication of mammalian ribosomal protein S3 in the processing of DNA damage. 777 13

Ionizing radiation and normal cellular respiration form reactive oxygen species that damage DNA and contribute to a variety of human disorders including tumor promotion and carcinogenesis. A major product of free radical DNA damage is the formation of 8-oxoguanine, which is a highly mutagenic base modification produced by oxidative stress. Here, Drosophila ribosomal protein S3 is shown to cleave DNA containing 8-oxoguanine residues efficiently, The ribosomal protein also contains an associated apurinic/apyrimidinic (AP) lyase activity, cleaving phosphodiester bonds via a beta,delta elimination reaction. The significance of this DNA repair activity acting on 8-oxoguanine is shown by the ability of S3 to rescue the H2O2 sensitivity of an Escherichia coli mutM strain (defective for the repair of 8-oxoguanine) and to abolish completely the mutator phenotype of mutM caused by 8-oxoguanine-mediated G-->T transversions. The ribosomal protein is also able to rescue the alkylation sensitivity of an E.coli mutant deficient for the AP endonuclease activities associated with exonuclease III (xth) and endonuclease IV (nfo), indicating for the first time that an AP lyase can represent a significant source of DNA repair activity for the repair of AP sites. These results raise the possibility that DNA repair may be associated with protein translation.
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PMID:A Drosophila ribosomal protein contains 8-oxoguanine and abasic site DNA repair activities. 864 Dec 96

Drosophila ribosomal protein PO was overexpressed in Escherichia coli to allow for its purification, biochemical characterization and to generate polyclonal antibodies for Western analysis. Biochemical tests were originally performed to see if overexpressed PO contained DNase activity similar to that recently reported for the apurinic/apyrimidinic (AP) lyase activity associated with Drosophila ribosomal protein S3. The overexpressed ribosomal protein was subsequently found to act on AP DNA, producing scissions that were in this case 5' of a baseless site instead of 3', as has been observed for S3. As a means of confirming that the source of AP endonuclease activity was in fact due to PO, glutathione S-transferase (GST) fusions containing a Factor Xa cleavage site between GST and PO were constructed, overexpressed in an E.coli strain defective for the major 5'-acting AP endonucleases and the fusions purified using glutathione-agarose affinity column chromatography. Isolated fractions containing purified GST-PO fusion proteins were subsequently found to have authentic AP endonuclease activity. Moreover, glutathione-agarose was able to deplete AP endonuclease activity from GST-PO fusion protein preparations, whereas the resin was ineffective in lowering DNA repair activity for PO that had been liberated from the fusion construct by Factor Xa cleavage. These results suggested that PO was a multifunctional protein with possible roles in DNA repair beyond its known participation in protein translation. In support of this notion, tests were performed that show that GST-PO, but not GST, was able to rescue an E.coli mutant lacking the major 5'-acting AP endonucleases from sensitivity to an alkylating agent. We furthermore show that GST-PO can be located in both the nucleus and ribosomes. Its nuclear location can be further traced to the nuclear matrix, thus placing PO in a subcellular location where it could act as a DNA repair protein. Other roles beyond DNA repair seem possible, however, since GST-PO also exhibited significant nuclease activity for both single- and double-stranded DNA.
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PMID:Drosophila ribosomal protein PO contains apurinic/apyrimidinic endonuclease activity. 893 86

The mammalian ribosomal protein S3 (rpS3) is a component of the 40S ribosomal subunit. It is known to function as a DNA repair enzyme, UV endonuclease III, which cleaves DNA that is irradiated by UV. It also has an endonuclease activity on AP DNA. In this report, the yeast ribosomal protein S3 (Rps3p) in S. cerevisiae was cloned, expressed in E. coli, and affinity-purified by 285 fold. Rps3p is composed of 240 amino acids and has a 78% amino acid similarity with the human counterpart that has 243 amino acids. The major difference in the amino acid sequence between the two proteins lies in most of the C-terminal 50 residues. Surprisingly, Rps3p only showed an endonuclease activity on AP DNA, but not on DNA that was irradiated with UV. The AP endonuclease activity of Rps3p was affected by pH, KCl, and beta-mercaptoethanol, but Triton X-100 and EDTA did not affect the enzyme activity. From these results, both the mammalian rpS3 and Rps3p appear to be involved in DNA damage processing, but in different modes.
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PMID:Yeast ribosomal protein S3 has an endonuclease activity on AP DNA. 1156 34

The human ribosomal protein S3 (rpS3) functions as a component of the 40S subunit and as a UV DNA repair endonuclease. This enzyme has an endonuclease activity for UV-irradiated and oxidatively damaged DNAs. DNA repair endonucleases recognize a variety of UV and oxidative base damages in DNA from E. coli to human cells. E. coli endonuclease III is especially known to have an iron-sulfur cluster as a co-factor. Here, we tried an electron paramagnetic resonance (EPR) method for the first time to observe a known iron-sulfur cluster signal from E. coli endonuclease III that was previously reported. We compared it to the human rpS3 in order to find out whether or not the human protein contains an iron-sulfur cluster. As a result, we succeeded in observing a Fe EPR signal that is apparently from an iron-sulfur cluster in the human rpS3 endonuclease. The EPR signal from the human enzyme, consisting of three major parts, is similar to that from the E. coli enzyme, but it has a distinct extra peak.
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PMID:Electron paramagnetic resonance study reveals a putative iron-sulfur cluster in human rpS3 protein. 1191 68

It is known that mammalian rpS3 functions as a DNA repair endonuclease and ribosomal protein S3. It was also observed that several ribosomal proteins or DNA repair enzymes are related to apoptosis. We report here a third function of rpS3, induction of apoptosis. The localization of green fluorescent protein (GFP)-rpS3 is changed to the nuclear membrane when lymphocytic cells undergo rpS3-induced apoptosis. Transient expression of GFP-rpS3 activates caspase-8/caspase-3 and sensitizes cytokine-induced apoptosis. Deletion analysis reveals that the two functions of rpS3, DNA repair and apoptosis, use independent functional domains.
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PMID:RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis. 1498 2

To generate data for comparative analyses of zygomycete mitochondrial gene expression, we sequenced mtDNAs of three distantly related zygomycetes, Rhizopus oryzae, Mortierella verticillata and Smittium culisetae. They all contain the standard fungal mitochondrial gene set, plus rnpB, the gene encoding the RNA subunit of the mitochondrial RNase P (mtP-RNA) and rps3, encoding ribosomal protein S3 (the latter lacking in R.oryzae). The mtP-RNAs of R.oryzae and of additional zygomycete relatives have the most eubacteria-like RNA structures among fungi. Precise mapping of the 5' and 3' termini of the R.oryzae and M.verticillata mtP-RNAs confirms their expression and processing at the exact sites predicted by secondary structure modeling. The 3' RNA processing of zygomycete mitochondrial mRNAs, SSU-rRNA and mtP-RNA occurs at the C-rich sequence motifs similar to those identified in fission yeast and basidiomycete mtDNAs. The C-rich motifs are included in the mature transcripts, and are likely generated by exonucleolytic trimming of RNA 3' termini. Zygomycete mtDNAs feature a variety of insertion elements: (i) mtDNAs of R.oryzae and M.verticillata were subject to invasions by double hairpin elements; (ii) genes of all three species contain numerous mobile group I introns, including one that is closest to an intron that invaded angiosperm mtDNAs; and (iii) at least one additional case of a mobile element, characterized by a homing endonuclease insertion between partially duplicated genes [Paquin,B., Laforest,M.J., Forget,L., Roewer,I., Wang,Z., Longcore,J. and Lang,B.F. (1997) Curr. Genet., 31, 380-395]. The combined mtDNA-encoded proteins contain insufficient phylogenetic signal to demonstrate monophyly of zygomycetes.
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PMID:Comparative mitochondrial genomics in zygomycetes: bacteria-like RNase P RNAs, mobile elements and a close source of the group I intron invasion in angiosperms. 1568 32

Mammalian rpS3, a ribosomal protein S3 with a DNA repair endonuclease activity, nicks heavily UV-irradiated DNA and DNA containing AP sites. RpS3 calls for a novel endonucleolytic activity on AP sites generated from pyrimidine dimers by T4 pyrimidine dimer glycosylase activity. This study revealed that rpS3 cleaves the lesions including AP sites, thymine glycols, and other UV damaged lesions such as pyrimidine dimers. This enzyme does not have a glycosylase activity as predicted from its amino acid sequence. However, it has an endonuclease activity on DNA containing thymine glycol, which is exactly overlapped with UV-irradiated or AP DNAs, indicating that rpS3 cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity acting as a base-damage-endonuclease. RpS3 cleaves supercoiled UV damaged DNA more efficiently than the relaxed counterpart, and the endonuclease activity of rpS3 was inhibited by MgCl2 on AP DNA but not on UV-irradiated DNA.
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PMID:Characterization of a wide range base-damage-endonuclease activity of mammalian rpS3. 1570 71

The human ribosomal protein S3 (rpS3) was expressed in E. coli using the pET-15b vector and the monoclonal antibodies (mAbs) were produced and characterized. A total of five hybridoma cell lines were established and the antibodies recognized a single band of molecular weight of 33 kDa on immunoblot with purified rpS3. When the purified rpS3 was incubated with the mAbs, the UV endonuclease activity of rpS3 was inhibited up to a maximum of 49%. The binding affinity of mAbs to rpS3 determined by using a biosensor technology showed that they have similar binding affinities. Using the anti-rpS3 antibodies as probes, we investigated the cross-reactivities of various other mammalian brain tissues and cell lines, including human. The immunoreactive bands on Western blots appeared to be the same molecular mass of 33 kDa in all animal species tested. They also appear to be extensively cross-reactive among different organs in rat. These results demonstrated that only one type of immunologically similar rpS3 protein is present in all of the mammalian brain tissues including human. Furthermore, these antibodies were successfully applied in immunohistochemistry in order to detect rpS3 in the gerbil brain tissues. Among the various regions in the brain tissues, the rpS3 positive neurons were predominantly observed in the ependymal cells, hippocampus and stantia nigra pars compacta. The different distributions of rpS3 in brain tissues reply that rpS3 protein may play an important second function in the neuronal cells.
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PMID:Immunohistochemical studies of human ribosomal protein S3 (rpS3). 2063 72

It has been shown previously that ribosomal protein S3 (rpS3) has an endonuclease activity, which is increased by protein kinase Cdelta (PKCdelta)-dependent phosphorylation. However, the reciprocal mechanism for rpS3 dephosphorylation is not known. In this study, we examined phosphatases involved in rpS3 dephosphorylation, and we determined that rpS3 is specifically dephosphorylated by protein phosphatase 2A (PP2A). By immunoprecipitation assay, rpS3 only interacted with PP2Ac but not with protein phosphatase 1. The interaction between rpS3 and PP2Ac occurred only in the nuclear fraction. Moreover, the PP2Ac association with rpS3 was identified in cells transfected with wild-type rpS3 but not with mutant rpS3 lacking PKCdelta phosphorylation sites. PP2A inhibition using okadaic acid induced rpS3 phosphorylation. The level of phosphorylated rpS3 in cells was decreased by the overexpression of PP2Ac and was increased by the down-regulation of PP2Ac. Taken together, these results suggest that oxidative stress regulates the phosphorylation status of nonribosomal rpS3 by both activating PKCdelta and blocking the PP2A interaction with rpS3.
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PMID:Phosphorylation status of nuclear ribosomal protein S3 is reciprocally regulated by protein kinase C{delta} and protein phosphatase 2A. 1945 93


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