Disease relevance of mutM

• mutM, a second mutator locus in Escherichia coli that generates G.C----T.A transversions [1].
• The formamidopyrimidine DNA glycosylase gene (fpg-L) of the Gram-positive microaerophilic bacterium Lactococcus lactis subsp. cremoris ML3 has been cloned, characterized and sequenced [2].
• Partial elimination of Fapy-7MeGua from phage DNA performed by its digestion with formamidopyrimidine-DNA glycosylase resulted in a 2-3-fold decrease of G-->T and G-->C transversions [3].
• Reduction of the toxicity and mutagenicity of aziridine in mammalian cells harboring the Escherichia coli fpg gene [4].

High impact information on mutM

• After subcloning a 1.4-kb fragment which contained the Fapy-DNA glycosylase gene (fpg+) was inserted in the plasmids pUC18 and pUC19 yielding pFPG50 and pFPG60 respectively [5].
• The nucleotide sequence of the fpg gene is composed of 809 base pairs and codes for a protein of 269 amino acids with a calculated mol. wt of 30.2 kd [5].
• E. coli (fpg mutY) was transformed by a yeast DNA library, and clones that showed a reduced spontaneous mutagenesis were selected [6].
• Cell-free extracts of E. coli (fpg mutY) harboring pYSB10 possess an enzymatic activity that cleaves a 34-mer oligonucleotide containing a single 8-oxoG opposite a cytosine (8-OxoG/C) [6].
• The 2,6-diamino-4-hydroxy-5N-formamidopyrimidine (Fapy)-DNA glycosylase of Escherichia coli, which is coded for by the fpg gene, excises purine bases with ring-opened imidazoles [7].

Chemical compound and disease context of mutM

• Deficiency of 8-hydroxyguanine DNA endonuclease activity and accumulation of the 8-hydroxyguanine in mutator mutant (mutM) of Escherichia coli [8].
• The Schiff base intermediate formed during this reaction between Escherichia coli Fpg and DNA was trapped by reduction with sodium borohydride, and the structure of the resulting covalently cross-linked complex was determined at a 2.1-A resolution [9].
• pBR322 plasmid DNA was treated with methylene blue plus visible light (MB-light) and tested for transformation efficiency in Escherichia coli mutants defective in either formamidopyrimidine-DNA glycosylase (Fpg protein) and/or UvrABC endonuclease [10].
• To examine the structural and dynamic changes that occur in solution when Fpg binds DNA, NMR spectroscopy was used to study Escherichia coli Fpg free in solution and bound to a double-stranded DNA oligomer containing 1,3-propanediol (13-PD), a non-hydrolyzable abasic-site analogue [11].
• In this work, we analyzed the cytotoxicity and mutagenesis induced after direct treatment of wild type and the DNA repair fpg and/or mutY deficient Escherichia coli strains with disodium 3,3'-(1,4-naphthylidene) diproprionate endoperoxide (NDPO(2)), which releases (1)O(2) by thermodissociation [12].

Biological context of mutM

• Strong mutator phenotypes of cells defective in both mutM and mutY genes or ones lacking mutT gene were completely suppressed under the anaerobic condition, indicative of an absence of hydroxyl radicals in the cells [13].
• The induction of the SOS response by hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide, formaldehyde, phenylhydrazine, and bleomycin was of almost the same magnitude between the parent strain and a mutM or soxRS mutant [14].
• An overproducing clone of Fapy-DNA glycosylase complements the original mutM strain that had been isolated after EMS mutagenesis [15].
• Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines from damaged DNA [9].
• This operon has transcription initiation sites upstream of radC, in the radC coding region, and immediately upstream of fpg [16].

Anatomical context of mutM

• Furthermore CHO cells expressing the fpg gene had the same resistance to the lethal effect of hydrogen peroxide as control cells [17].

Associations of mutM with chemical compounds

• In comparison to the parent strain WP2s, however, the introduction of mutM, mutY, or soxRS mutations, in any combination, did not make the strain hypersensitive in terms of mutability (i.e. mutation induction at relatively low doses) to hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide, or phenylhydrazine [14].
• In this report, we have characterized mutM mutant with respect to its ability to repair 8-hydroxyguanine (oh8Gua) in DNA [8].
• Formamidopyrimidine-DNA glycosylase (Fpg) is a primary participant in the repair of 8-oxoguanine, an abundant oxidative DNA lesion [18].
• The excision of hepsulfam-induced DNA adducts has been determined by treatment with homogeneous recombinant bacterial, rat and human 3-methyladenine DNA glycosylases and successive treatments by formamidopyrimidine-DNA glycosylase [19].
• MS/MS analysis of the purified proteolytic fragments suggests that lysine 56 of Fpg and lysine 249 of hOgg1 cross-link to the phosphate located 3' to the 8-oxoG residue [20].

Regulatory relationships of mutM

• The influence of formamidopyrimidine-DNA glycosylase on the spontaneous and gamma-radiation-induced mutation spectrum of the lacZ alpha gene [21].

Other interactions of mutM

• The locus, mutM, mapped near the cysE locus, which is at 81 min on the genetic map [1].
• The frequencies of targeted G-->T transversions increased markedly in mutY strains, while this mutagenic event was not affected in mutM or mutS strains [22].
• This strongly supports a role for NER in the repair of oxidative base damage in yeast, and differs from similar experiments carried out in E. coli, where transformation efficiency is only reduced in mutants defective in both fpg and uvrA [23].
• To evaluate the relative importance of Fpg (Fapy) glycosylase (an enzyme known to remove oxidized bases) and the DNA damage-inducible UvrABC excinuclease in recovery from near-UV-induced stress, we have constructed fpg- and uvrA- derivatives of Escherichia coli and tested the response (survival) of these strains to both UVA and far-UV radiation [24].
• The end of an open reading frame present upstream of the recA gene shows strong homology with formamidopyrimidine-DNA-glycosylase, a protein involved in DNA repair [25].

Analytical, diagnostic and therapeutic context of mutM

• Site-specific mutagenesis analysis of Fpg binding to DNA substrate confirms the conclusions of our approach [20].

References