Distinct substrate preference of human and mouse N-methylpurine-DNA glycosylases.
N-Methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair protein, removes several N-alkylpurine adducts, hypoxanthine, cyclic ethenoadducts of adenine, guanine and cytosine and 8-oxoguanine from DNA. The recombinant human and mouse MPGs, purified from Escherichia coli, show a significant difference in substrate preference. While both proteins prefer 3-methyladenine over other N-alkylpurines in DNA, the mouse MPG removes 7-methylguanine and 3-methylguanine at an approximately 2- to 3-fold higher rate than the human protein when adjusted for equal activity for the release of 3-methyladenine from DNA. Hybrid recombinant proteins containing N-terminal and C-terminal halves of the human and mouse glycosylases were partially purified from MPG-negative E.coli. Their substrate preferences suggest that the N-terminal half is more critical for the recognition of 3-methylguanine and 7-methylguanine.
Sealy Center for Molecular Science, Department of Human Biological Chemistry and Genetics, University of Texas Medical Center, Galveston 77555, USA.
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D000818:Animals; D045647:DNA Glycosylases; D004260:DNA Repair; D006801:Humans; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013045:Species Specificity; D013379:Substrate Specificity
D011994:Recombinant Proteins; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases