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Gene Review

MAG1  -  Mag1p

Saccharomyces cerevisiae S288c

Synonyms: 3-methyladenine DNA glycosidase, 3MEA DNA glycosylase, DNA-3-methyladenine glycosylase, MAG, YER142C
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Disease relevance of MAG1


High impact information on MAG1

  • 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) [5].
  • We previously cloned a DNA fragment from Saccharomyces cerevisiae that suppressed the alkylation sensitivity of Escherichia coli glycosylase deficient mutants and we showed that it apparently contained a gene for 3-methyl-adenine DNA glycosylase (MAG) [6].
  • The MAG gene, which we mapped to chromosome V, is not allelic with any of the RAD genes and appears to be allelic to the unmapped MMS-5 gene [6].
  • Moreover, Rpa appears to bind the MAG URS1-like elements found upstream of 11 other DNA repair and DNA metabolism genes [7].
  • ANPG protein, APDG protein, and MAG protein--the 3-methyladenine DNA glycosylases of human, rat, and yeast origin, respectively--were also able to release hypoxanthine from various DNA substrates containing dIMP residues [8].

Chemical compound and disease context of MAG1


Biological context of MAG1

  • MMS-induced DNA lesions include base damages such as 3-methyl adenine and 7-methyl guanine, and these lesions are removed in yeast by the alternate competing pathways of base excision repair (BER), which is initiated by the action of MAG1-encoded N-methyl purine DNA glycosylase, and NER [11].
  • To accomplish this, we have deleted one of the genes essential for NER in yeast, namely, RAD14, both in the context of an otherwise DNA repair-proficient strain (Deltarad14) and in a BER-defective isogenic derivative lacking the MAG1 gene (Deltamag1rad14) [12].
  • Deletion of the MAG1 DNA glycosylase gene suppresses alkylation-induced killing and mutagenesis in yeast cells lacking AP endonucleases [13].
  • Two alternative cell cycle checkpoint pathways differentially control DNA damage-dependent induction of MAG1 and DDI1 expression in yeast [14].
  • The MAG1 gene encodes a 3-methyladenine DNA glycoslyase, which is involved in DNA alkylation repair in Saccharomyces cerevisiae [15].

Anatomical context of MAG1

  • Electron microscopy revealed that mag1 seeds mis-sort storage proteins by secreting them from cells. mag1 seeds have smaller protein storage vacuoles in the seeds than do wild-type seeds [16].

Associations of MAG1 with chemical compounds

  • Interestingly, this sensitivity can be reduced up to 2500-fold by deleting the MAG1 3-methyladenine DNA glycosylase gene, suggesting that Mag1 not only removes lethal base lesions, but also benign lesions and possibly normal bases, and that the resulting AP sites are highly toxic to the cells [13].
  • We previously reported that yeast cells deficient in the two AP endonucleases (apn1 apn2 double mutant) are extremely sensitive to killing by a model DNA alkylating agent methyl methanesulfonate (MMS) and that this sensitivity can be reduced by deleting the MAG1 3-methyladenine DNA glycosylase gene [17].
  • This rescuing effect appears to be specific for DNA alkylation damage, since the mag1 mutation reduces killing effects of two other DNA alkylating agents, but does not alter the sensitivity of apn cells to killing by UV, gamma-ray or H(2)O(2) [13].
  • Furthermore, MAG1 and DDI1 respond differently in the presence of the protein synthesis inhibitor cycloheximide, suggesting that these two genes are regulated by different mechanisms in the absence of de novo protein synthesis [18].
  • 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 [19].

Other interactions of MAG1

  • However, mag1 and apn1 mutants that are also defective in nucleotide excision repair are extremely sensitive to MMS-induced killing and the effects are synergistic [20].
  • In order to understand how damage checkpoints control the expression of DNA damage-inducible genes, the transcript level of two closely clustered genes, MAG1 and DDI1, was examined in a number of checkpoint mutants [14].
  • We previously reported that MAG1 induction was abolished in pol2 and rad53 mutants, but not in the mec1-1 mutant [14].
  • We show that cells lacking Mag1 have increased susceptibility to methylation-induced recombination, and that disruption of nucleotide excision repair (NER; rad4) in mag1 cells increases cellular susceptibility to these events [2].
  • The MAG1* 3-methyladenine DNA glycosylase gene is closely linked to the SPT15 TATA-binding TFIID gene on chromosome V-R in Saccharomyces cerevisiae [15].

Analytical, diagnostic and therapeutic context of MAG1

  • Here we establish the identity of the MAG gene by sequence analysis and describe its in vivo function and expression in yeast cells [6].


  1. Generation of a strong mutator phenotype in yeast by imbalanced base excision repair. Glassner, B.J., Rasmussen, L.J., Najarian, M.T., Posnick, L.M., Samson, L.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. The S. cerevisiae Mag1 3-methyladenine DNA glycosylase modulates susceptibility to homologous recombination. Hendricks, C.A., Razlog, M., Matsuguchi, T., Goyal, A., Brock, A.L., Engelward, B.P. DNA Repair (Amst.) (2002) [Pubmed]
  3. Cloning and characterization of a cDNA encoding a 3-methyladenine DNA glycosylase from the fission yeast Schizosaccharomyces pombe. Memisoglu, A., Samson, L. Gene (1996) [Pubmed]
  4. Excision repair of nitrogen mustard-DNA adducts in Saccharomyces cerevisiae. McHugh, P.J., Gill, R.D., Waters, R., Hartley, J.A. Nucleic Acids Res. (1999) [Pubmed]
  5. Primary sequence and biological functions of a Saccharomyces cerevisiae O6-methylguanine/O4-methylthymine DNA repair methyltransferase gene. Xiao, W., Derfler, B., Chen, J., Samson, L. EMBO J. (1991) [Pubmed]
  6. Saccharomyces cerevisiae 3-methyladenine DNA glycosylase has homology to the AlkA glycosylase of E. coli and is induced in response to DNA alkylation damage. Chen, J., Derfler, B., Samson, L. EMBO J. (1990) [Pubmed]
  7. Replication protein A binds to regulatory elements in yeast DNA repair and DNA metabolism genes. Singh, K.K., Samson, L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. Excision of hypoxanthine from DNA containing dIMP residues by the Escherichia coli, yeast, rat, and human alkylpurine DNA glycosylases. Saparbaev, M., Laval, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  9. Protection against chloroethylnitrosourea cytotoxicity by eukaryotic 3-methyladenine DNA glycosylase. Matijasevic, Z., Boosalis, M., Mackay, W., Samson, L., Ludlum, D.B. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  10. Purification and properties of the alkylation repair DNA glycosylase encoded the MAG gene from Saccharomyces cerevisiae. Bjørås, M., Klungland, A., Johansen, R.F., Seeberg, E. Biochemistry (1995) [Pubmed]
  11. Yeast RAD26, a homolog of the human CSB gene, functions independently of nucleotide excision repair and base excision repair in promoting transcription through damaged bases. Lee, S.K., Yu, S.L., Prakash, L., Prakash, S. Mol. Cell. Biol. (2002) [Pubmed]
  12. Nucleotide excision repair defect influences lethality and mutagenicity induced by Me-lex, a sequence-selective N3-adenine methylating agent in the absence of base excision repair. Monti, P., Iannone, R., Campomenosi, P., Ciribilli, Y., Varadarajan, S., Shah, D., Menichini, P., Gold, B., Fronza, G. Biochemistry (2004) [Pubmed]
  13. Deletion of the MAG1 DNA glycosylase gene suppresses alkylation-induced killing and mutagenesis in yeast cells lacking AP endonucleases. Xiao, W., Chow, B.L., Hanna, M., Doetsch, P.W. Mutat. Res. (2001) [Pubmed]
  14. Two alternative cell cycle checkpoint pathways differentially control DNA damage-dependent induction of MAG1 and DDI1 expression in yeast. Zhu, Y., Xiao, W. Mol. Genet. Genomics (2001) [Pubmed]
  15. The MAG1* 3-methyladenine DNA glycosylase gene is closely linked to the SPT15 TATA-binding TFIID gene on chromosome V-R in Saccharomyces cerevisiae. Xiao, W., Penugonde, V., Rank, G.H. Yeast (1994) [Pubmed]
  16. AtVPS29, a Putative Component of a Retromer Complex, is Required for the Efficient Sorting of Seed Storage Proteins. Shimada, T., Koumoto, Y., Li, L., Yamazaki, M., Kondo, M., Nishimura, M., Hara-Nishimura, I. Plant Cell Physiol. (2006) [Pubmed]
  17. Involvement of two endonuclease III homologs in the base excision repair pathway for the processing of DNA alkylation damage in Saccharomyces cerevisiae. Hanna, M., Chow, B.L., Morey, N.J., Jinks-Robertson, S., Doetsch, P.W., Xiao, W. DNA Repair (Amst.) (2004) [Pubmed]
  18. UAS(MAG1), a yeast cis-acting element that regulates the expression of MAG1, is located within the protein coding region of DDI1. Liu, Y., Dai, H., Xiao, W. Mol. Gen. Genet. (1997) [Pubmed]
  19. A common element involved in transcriptional regulation of two DNA alkylation repair genes (MAG and MGT1) of Saccharomyces cerevisiae. Xiao, W., Singh, K.K., Chen, B., Samson, L. Mol. Cell. Biol. (1993) [Pubmed]
  20. Synergism between yeast nucleotide and base excision repair pathways in the protection against DNA methylation damage. Xiao, W., Chow, B.L. Curr. Genet. (1998) [Pubmed]
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