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 ethenoadd ucts of adenine, guanine and cytosine and 8-oxoguanine from DNA, The r ecombinant 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 similar to 2- to 3- fold higher rate than the human protein when adjusted for equal activi ty for the release of 3-methyladenine from DNA, Hybrid recombinant pro teins containing N-terminal and C-terminal halves of the human and mou se glycosylases were partially purified from MPG-negative E. coli. The ir substrate preferences suggest that the N-terminal half is more crit ical for the recognition of 3-methylguanine and 7-methylguanine.