Disease relevance of mutY

• Strains of Escherichia coli carrying the mutY mutation lack a mismatch correction glycosylase that removes adenines from various mismatch situations [1].
• The mutT, mutM, and mutY genes of the GO system of the Pseudomonas aeruginosa PAO1 strain have been characterized by cloning, sequencing, and complementation analysis [2].
• Antimutator role of the DNA glycosylase mutY gene in Helicobacter pylori [3].

High impact information on mutY

• We now show that when trpA23 mutY bacteria are held under tryptophan starvation conditions the tryptophan-independent mutants that arise include small in-frame deletions in addition to transversions [1].
• Extracts prepared from mutY/mutM E. coli expressing mOgg1 contain an activity that excises 8-oxoguanine from DNA and a beta-lyase activity that nicks DNA 3' to the lesion [4].
• In addition, we have isolated a strain with a chromosomal mutation that suppresses the mutY phenotype and found that this suppressor also overexpresses MutM [5].
• We find that the mutator phenotype of a mutY strain can be fully complemented by overexpressing MutM protein (Fpg protein) from a plasmid clone [5].
• The Escherichia coli adenine DNA glycosylase, MutY, plays an important role in the maintenance of genomic stability by catalyzing the removal of adenine opposite 8-oxo-7,8-dihydroguanine or guanine in duplex DNA [6].

Chemical compound and disease context of mutY

• The mutY gene of Escherichia coli, which codes for an adenine glycosylase that excises the adenine of a G-A mispair, has been cloned and sequenced [7].
• 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 [8].

Biological context of mutY

• Here, we demonstrate that the mutant MutY(Delta26-134), which lacks the six-helix barrel domain, cannot complement the mutator phenotype of a mutY mutant in vivo [9].
• In contrast, the ung and mutY mutants did not show higher frequencies of intergenomic recombination or greater sensitivity to UV-induced DNA damage than the wild type [3].
• The H. pylori mutY open reading frame contains an eight-adenine homonucleotide tract; we provide evidence that this is subject to slipped-strand mispairing, leading to frameshifts that eliminate gene function [3].
• In strains IC3894 (mutY) and IC3981 (mutY mutM), lacking mutagenesis proteins, SOS-independent revertants arose almost exclusively via G:C-T:A transversions probably derived from oxidatively damaged 8-oxoguanine/adenine mispairs [10].
• The DNA sequence of a 2.3-kb fragment containing the micA gene has been determined [11].

Associations of mutY with chemical compounds

• 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 [12].
• These G:C to T:A transversions observed in the mutY strain were suggested to be the result of mispairing of oh8Gua with adenine [13].
• Using 8-oxo-dGTP-induced mutagenesis, transitions especially A:T --> G:C were predominant in the wild type and mutY strains [14].
• MutY is an adenine-DNA glycosylase with specificity for mismatches involving 8-oxoguanine (oG.A) or guanine (G.A) [15].

Other interactions of mutY

• Spontaneous mutation frequencies of JP26 mutY mutants, assessed by rifampin resistance, were consistently higher (26-fold) than that of the wild type, whereas the ung and xthA mutants showed smaller increases [3].
• Repair of heteroduplex DNA containing an A/G mismatch in a mutL background requires the Escherichia coli mutY gene function [16].

Analytical, diagnostic and therapeutic context of mutY

• The observation that oG specificity derives almost exclusively from the C-terminal domain of MutY adds credence to the sequence analyses and suggests that specificity for oG.A mismatches was acquired by fusion of a MutT-like protein onto the core catalytic domain of an adenine-DNA glycosylase [15].

References