Disease relevance of MGT1

• We previously cloned a yeast DNA fragment that, when fused with the bacterial lacZ promoter, produced O6-methylguanine DNA repair methyltransferase (MGT1) activity and alkylation resistance in Escherichia coli (Xiao et al., EMBO J. 10,2179) [1].

High impact information on MGT1

• Two additional proteins known to function in mtDNA recombination, Abf2p and Mgt1p, are also required for parsing mtDNA into a larger number of nucleoids, although expression of these proteins is not under general amino acid control [2].
• MGT1 transcript levels are not increased in response to DNA alkylation damage, nor is the MGT1 MTase involved in the regulation of the yeast 3-methyladenine DNA glycosylase gene (MAG) [3].
• S.cerevisiae mutants bearing an insertion in the MGT1 gene lacked DNA MTase activity and were very sensitive to alkylation induced killing and mutation [3].
• The cloned yeast fragment was mapped to chromosome IV and DNA sequencing identified an open reading frame, designated MGT1, which encodes a 188 amino acid protein with a molecular weight of 21,500 daltons [3].
• The Saccharomyces cerevisiae MGT1 DNA repair methyltransferase gene: its promoter and entire coding sequence, regulation and in vivo biological functions [1].

Biological context of MGT1

• One of the MAG URS elements matches a decamer consensus sequence present in the promoters of 11 other S. cerevisiae DNA repair and metabolism genes, including the MGT1 gene, which encodes an O6-methylguanine DNA repair methyltransferase [4].
• The MGT1 promoter was fused to a lacZ reporter gene to study how MGT1 expression is controlled [1].
• Our work indicates that MGT1 plays a crucial role in the competition for inheritance between hypersuppressive p- mtDNAs and the p+ mitochondrial genome [5].
• However, the rev3 deletion does not affect methylation damage-induced killing and mutagenesis of the mgt1 mutant, suggesting that endogenous alkyl lesions may be different from O6-MeG [6].
• When one haploid parent carries the mgt1 allele, transmission of p- mtDNA is substantially reduced [5].

Anatomical context of MGT1

• Finally we show that mgt1 S.cerevisiae has a higher rate of spontaneous mutation than wild type cells, indicating that there is an endogenous source of DNA alkylation damage in these eukaryotic cells and that one of the in vivo roles of MGT1 is to limit spontaneous mutations [1].
• Since CCE1 is allelic to MGT1, a gene required for the highly biased transmission of petite mitochondrial DNA in crosses between rho+ and hypersuppressive rho- cells, it seems likely that the CCE1 endonuclease functions within mitochondria [7].
• When crosses were performed in the mgt1/cce1 background, the parental molecules interacted in zygotes and underwent homologous recombination but wild-type and intergenic-deletion alleles were transmitted with equal frequencies [8].

Associations of MGT1 with chemical compounds

• Upon galactose induction, the PGAL1-MGMT transformant had about 40-fold MTase activity compared to the wild-type strain [9].
• The expression of yeast MGMT gene is decreased when cells reach stationary phase and cannot be induced by the pretreatment with alkylating agents, methylmethanesulfonate (MMS) or N-methyl-N'-nitroso-N-nitrosoguanidine (MNNG) [10].
• The MGMT gene from KOD1 (mgtk) comprises 522 nucleotides, encoding 174 amino acid residues; its product shows considerable similarity to the corresponding mammalian, yeast and bacterial enzymes, especially around putative methyl acceptor sites [11].
• The cloned KOD1 MGMT gene was overexpressed using the T7 RNA polymerase expression system, and the recombinant protein was purified by ammonium sulfate fractionation, heat treatment, ion-exchange chromatography and gel filtration chromatography [11].

Analytical, diagnostic and therapeutic context of MGT1

• Based on PCR amplification using primers derived from conserved amino acid sequences of MGMTs from 11 species, we isolated the DNA region coding for MGMT from the hyperthermophilic archaeon Pyrococcus sp. KOD1 [11].

References