A new member of the endonuclease III family of DNA repair enzymes that removes methylated purines from DNA.
DNA is constantly exposed to endogenous andexogenous alkylating agents that can modify its bases,resulting in mutagenesis in the absence of DNA repair [1,2]. Alkylation damage is removed by the action of DNA glycosylases, which initiate the base excision repair pathway and protect the sequence information of the genome [3-5]. We have identified a new class of methylpurine DNA glycosylase, designated MpgII, that is a member of the endonuclease III family of DNA repair enzymes. We expressed and purified MpgII from Thermotoga maritima and found that the enzyme releases both 7-methylguanine and 3-methyladenine from DNA. We cloned the MpgII genes from T. maritima and from Aquifex aeolicus and found that both genes could restore methylmethanesulfonate (MMS) resistance to Escherichia coli alkA tagA double mutants, which are deficient in the repair of alkylated bases. Analogous genes are found in other Bacteria and Archaea and appear to be the only genes coding for methylpurine DNA glycosylase activity in these organisms. MpgII is the fifth member of the endonuclease III family of DNA repair enzymes, suggesting that the endonuclease III protein scaffold has been modified during evolution to recognize and repair a variety of DNA damage.
Begley
T J
TJ
Department of Biological Sciences, SUNY at Albany, 1400 Washington Avenue, Albany, New York, 12222, USA.
Haas
B J
BJ
Noel
J
J
Shekhtman
A
A
Williams
W A
WA
Cunningham
R P
RP
D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D004249:DNA Damage; D045647:DNA Glycosylases; D019175:DNA Methylation; D004260:DNA Repair; D004269:DNA, Bacterial / Q000187:drug effects / Q000378:metabolism*; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D020124:Thermotoga maritima / Q000201:enzymology / Q000235:genetics
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D008741:Methyl Methanesulfonate; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases