Disease relevance of MPG

• The epsilonA residues are excised by the human and the Escherichia coli 3-methyladenine-DNA glycosylases (ANPG and AlkA proteins, respectively), but the enzymes repairing epsilonC residues have not yet been described [1].
• CONCLUSIONS: (a) Me-lex is cytotoxic in human glioma cells and AAG promotes resistance, indicating that 3-meA is a lethal lesion in these cells [2].
• Activity of N-methylpurine-DNA glycosylase (MPG) was not significantly altered in any of the drug-resistant melanoma cells [3].
• However, the MPG expression of the nucleus in malignant epithelial tumors, both serous and mucinous type, disappeared [4].
• The genetic polymorphisms in the coding exons 2, 3 and 4 of MPG and in the enhancer region of MGMT were searched for in DNA samples from a group of 33 non-small-cell lung cancer (NSCLC) patients from Poland [5].

Psychiatry related information on MPG

• For Wellington-Dufferin, the leading causes of YHLL were concentrated in the program areas of chronic disease, injury, and substance abuse and included four areas not addressed in the MPG (suicide, depression, dementia, and osteoarthritis) [6].
• OBJECTIVE: This study was carried out to examine sociopsychopathological predictors of prospective observed suicide attempts in bulimic women purging type without comorbid major depression (BNG) at the time of study entry and in woman with major depression without comorbid eating disorder at the time of study entry (MDG) [7].

High impact information on MPG

• We report here that the complete nucleotide sequence of a beta E-gene revealed the expected GAG leads to AAG change in codon 26 but no other mutations [8].
• We recently demonstrated that the molecular lesion in a Chinese patient with nonfunctional beta-globin mRNA was due to the mutation of the normal lysine codon AAG at amino acid 17 to the amber terminator codon UAG, which prematurely terminates the beta-globin chain [9].
• Certain of the biological properties of AAG are related to its sialic acid content; thus, clearance and immunogenicity of AAG are markedly increased on desialisation [10].
• AAG has the ability to inhibit certain lymphocyte re-activities including blastogenesis in response to concanavalin A, phytohaemagglutinin and allogeneic cells, and these inhibitory effects are enhanced in association with desialisation [10].
• We report that desialisation of AAG is associated with increased expression of activity inhibitory to the platelet aggregation otherwise observed on stimulation with ADP, collagen or thrombin [10].

Chemical compound and disease context of MPG

• The human cDNA-encoded MPG releases 3-methyladenine, 7-methylguanine, and 3-methylguanine from DNA and thus has a substrate range similar to that of the indigenous enzyme and the E. coli AlkA protein [11].
• Overexpression of the mitochondrially targeted MPG dramatically increased the breast cancer cells' sensitivity to methyl methanesulfonate [12].
• Pretreatment with ceramide reduced lactate dehydrogenase release at the end of the simulated ischemia but this cytoprotective effect was lost in the presence of MPG [13].
• Methoxyamine reduction of cell survival is significantly greater in cells overexpressing MPG than in control cells, suggesting a heightened production of AP sites that, if made persistent, results in increased cellular toxicity [14].
• Healthy adult Swiss mice were injected intraperitoneally (i.p.) with 50 micrograms kg-1 body weight of Ot or Vc; 20 mg kg-1 of MPG; 150 mg kg-1 of WR-2721 or double distilled water (DDW) [15].

Biological context of MPG

• These data suggest that MBD1 cooperates with MPG for transcriptional repression and DNA repair [16].
• MPG itself actively represses transcription and has a synergistic effect on gene silencing together with MBD1 [16].
• In this report, we show that the hHR23A and -B also interact with the MPG protein and can serve as accessory proteins for DNA damage recognition in base excision repair [17].
• Our studies suggest that recruitment of MPG to ERE-containing genes influences transcription and plays a role in maintaining integrity of the genome by recruiting DNA repair proteins to actively transcribing DNA [18].
• In turn, MPG dramatically stabilized the interaction of ERalpha with ERE-containing oligos, decreased p300-mediated acetylation of the receptor, and reduced transcription of simple and complex ERE-containing reporter plasmids in a dose-dependent manner [18].

Anatomical context of MPG

• A hamster cell line variant isolated as being resistant to methylmethane sulfonate does not have a higher level of MPG mRNA than the parent cell line [11].
• Although the 1.1-kilobase mRNAs of MPG from human and rodents are similar in size, liver and cultured cells of rat have much lower levels of MPG mRNA than do human and mouse cells [11].
• RESULTS: MPG mRNA expression in epithelial ovarian tumor and spermatogenic arrest testis tissues was slightly higher than in normal ovarian and testicular tissues, respectively [4].
• MPG was stained mostly in the nucleus and faintly-stained in the cytoplasm of normal coelomic epithelium as well as in benign epithelial ovarian tumors [4].
• In a normal ovary, immunostaining for MPG was observed in the nucleus of oocyte, granulosa and stromal cells [4].

Associations of MPG with chemical compounds

• (e) AAG and Ape1 inhibitors may be useful in targeting alkylating agent resistance [2].
• Furthermore, the MPG.hHR23 protein complex elevates the rate of MPG protein-catalyzed excision from hypoxanthine-containing substrates [17].
• We have identified a novel interaction between ERalpha and the DNA repair protein 3-methyladenine DNA glycosylase (MPG) thereby providing a functional link between gene expression and DNA repair [18].
• N-Methylpurine-DNA glycosylase (MPG) initiates base excision repair in DNA by removing a wide variety of alkylated, deaminated, and lipid peroxidation-induced purine adducts [19].
• These results altogether suggest that Mg(2+) inhibits MPG activity by abrogating substrate binding [19].

Physical interactions of MPG

• We report here that methylation-mediated transcriptional repressor methylated DNA-binding domain 1 (MBD1) interacts with methylpurine-DNA glycosylase (MPG), which excises damaged bases from substrate DNA [16].

Other interactions of MPG

• We hypothesize that MBD1 functions as a reservoir for MPG and senses the base damage in chromatin[16]
• Expression of PADPRP or molecules involved in the BER system [3-methylpurine-DNA glycosylase (MPG) and X-ray repair cross-complementing 1 (XRCC1)], have been explored [20].
• Frequencies of the "A" and "G" alleles (MGMT codon 178, AAG and AGG, respectively) were 0.91 and 0.09, respectively [21].
• Steady-state mRNA levels of MPG, human Nth homologue (NTH), and uracil-DNA glycosylase (UDG), DNA glycosylases, and human AP site-specific endonuclease (APE), an endonuclease incising DNA at abasic sites, are cell cycle dependent [22].
• Under the same conditions of treatment, exerting only a weak toxic effect, MPG and DNA ligase I mRNA levels were not enhanced, whereas the amounts of APE and Pol beta mRNA transiently increased by approximately 2-fold after X-ray and MNNG treatment, respectively [23].

Analytical, diagnostic and therapeutic context of MPG

• Increase of PADPRP or MPG transcripts was found after treatment with TZM alone or combined with PADPRP inhibitor [20].
• RESULTS: MPG mRNA expression in RT-PCR was slightly higher in astrocytic tumor tissues than in brain tissues adjacent to tumor and in astrocytic tumor tissues, regardless of the tumor grades [24].
• The expression and intracellular localization of MPG protein was determined by immunohistochemistry [24].
• MATERIALS AND METHODS: MPG mRNA expression and localization in astrocytic tumors and tumor-adjacent brain tissues was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNA in situ hybridization [24].
• We have used pH dependencies, site-directed mutagenesis, and a variety of substrates to investigate the catalytic mechanism of AAG [25].

References