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.