Nucleic Acids Research, Vol 26, Issue 17 4034-4041, Copyright © 1998 by Oxford University Press
F Miao, M Bouziane and TR O'Connor
Methylpurine-DNA glycosylases (MPG proteins, 3-methyladenine-DNA
glycosylases) excise numerous damaged bases from DNA during the first step
of base excision repair. The damaged bases removed by these proteins
include those induced by both alkylating agents and/or oxidizing agents.
The intrinsic kinetic parameters (k(cat) and K(m)) for the excision of
hypoxanthine by the recombinant human MPG protein from a 39 bp
oligodeoxyribonucleotide harboring a unique hypoxanthine were determined.
Comparison with other reactions catalyzed by the human MPG protein suggests
that the differences in specificity are primarily in product release and
not binding. Analysis of MPG protein binding to the 39 bp
oligodeoxyribonucleotide revealed that the apparent dissociation constant
is of the same order of magnitude as the K(m) and that a 1:1 complex is
formed. The MPG protein also forms a strong complex with the product of
excision, an abasic site, as well as with a reduced abasic site. DNase I
footprinting experiments with the MPG protein on an
oligodeoxyribonucleotide with a unique hypoxanthine at a defined position
indicate that the protein protects 11 bases on the strand with the
hypoxanthine and 12 bases on the complementary strand. Competition
experiments with different length, double-stranded, hypoxanthine-containing
oligodeoxyribonucleotides show that the footprinted region is relatively
small. Despite the small footprint, however, oligodeoxyribonucleotides
comprising <15 bp with a hypoxanthine have a 10-fold reduced binding
capacity compared with hypoxanthine-containing oligodeoxyribonucleotides
>20 bp in length. These results provide a basis for other structural
studies of the MPG protein with its targets.
ARTICLES
Interaction of the recombinant human methylpurine-DNA glycosylase (MPG protein) with oligodeoxyribonucleotides containing either hypoxanthine or abasic sites
Beckman Research Institute, City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010, USA.
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