Disease relevance of mutY

• In Escherichia coli the mutY (or micA)-dependent DNA mismatch repair pathway can convert A degrees G and A degrees C mismatches to C.G and G.C base pairs, respectively, through a short repair-tract mechanism [1].
• Antimutator role of the DNA glycosylase mutY gene in Helicobacter pylori [2].
• The mutY homolog gene (mutY(Dr)) from Deinococcus radiodurans encodes a 39.4-kDa protein consisting of 363 amino acids that displays 35% identity to the Escherichia coli MutY (MutY(Ec)) protein [3].

High impact information on mutY

• Inherited defects of base excision repair have not been associated with any human genetic disorder, although mutations of the genes mutM and mutY, which function in Escherichia coli base excision repair, lead to increased transversions of G:C to T:A [4].
• Mutations in the mutY gene of Escherichia coli confer hypermutability reflecting G.C to T.A transversion mutations and result in a deficiency in methyl-independent G-A to G.C mismatch correction [5].
• Mutations disabling the first system result in a mutator phenotype that may be identical to mutY [6].
• We propose that the mutY product functions at a late stage of a pathway that excludes A-G mispairs during chromosome replication and that involves the function of the mutT gene product [7].
• 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 [8].

Chemical compound and disease context of mutY

• Mutations in the mutY gene of Escherichia coli enhance the frequency of targeted G:C-->T:a transversions induced by a single 8-oxoguanine residue in single-stranded DNA [9].

Biological context of mutY

• The amino acid sequence encoded by the mutB gene is 91% homologous to that encoded by the E. coli mutY gene [10].
• In addition, H. pylori mutY mutants are only 30% as efficient as wild-type in colonizing the stomach of mice, indicating that H. pylori MutY plays a significant role in oxidative DNA damage repair in vivo [11].
• 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 [2].
• This operon has transcription initiation sites upstream of mutY, in the mutY coding region, and immediately upstream of nupG [12].
• Derivatives of E. coli WP2s (uvrA trpE) defective in 7,8-dihydro-8-oxoguanine (8-OG) DNA glycosylase activity (mutM), MutY glycosylase activity on an A:8-OG mispair (mutY), and/or an adaptive response to oxidative stress by superoxide (soxRS) were constructed to compare the mutability to various reactive oxygen-generating compounds [13].

Associations of mutY with chemical compounds

• A-G mispairs that persist after passage of the replication fork would contain guanine on the template strand and thus be processed to C.G base pairs by the mutY-dependent repair system [7].
• Overexpression of the MutS repair protein significantly decreased the rate of lacZ GC --> TA transversion mutation in stationary-phase and exponentially growing bacteria and in mutY and mutM mutants, which accumulate mismatches between 8-oxoguanine (8-oxoG) and adenine residues in DNA [14].
• But mutY expression was higher in glucose- or ammonia-limited chemostats than in nutrient-excess batch culture, so mutY was not downregulated by nutrient limitation [15].

Analytical, diagnostic and therapeutic context of mutY

• Based on PCR analysis of the region within and around mutY, isolates from three individual populations contained deletions extending at least 2 kb upstream of mutY and more than 5 kb downstream [15].

References