1022-7954/05/4106- © 2005 Pleiades Publishing, Inc.
Russian Journal of Genetics, Vol. 41, No. 6, 2005, pp. 583–592. Translated from Genetika, Vol. 41, No. 6, 2005, pp. 725–735.
Original Russian Text Copyright © 2005 by Korolev.
Under normal conditions, endogenous processes are
the major source of damage to genetic material of the
cell in living organisms. These processes include (1) DNA
oxidation by peroxides, which are generated as a result
of normal aerobic metabolism; (2) spontaneous deami-
nation of DNA bases; and (3) DNA methylation with S-
adenosylmethionine. In addition, DNA bases may be
damaged by a great variety of exogenous factors. Most
of the resulting lesions prevent or dramatically deceler-
ate DNA replication, thereby exerting a cytotoxic
effect. Some lesions give origin to mutations as DNA is
processed by the replication machinery.
Several enzymatic mechanisms are responsible for
excision of damaged bases in the living cell. With most
types of damaged bases, excision repair is initiated by
DNA glycosylases, speciﬁc repair enzymes that cata-
lyze hydrolysis of the N-glycoside bond between a
damaged or mispaired base and the DNA sugar–phos-
phate backbone. The type of DNA repair initiated by
DNA glycosylases is known as base excision repair,
because the glycosylase reaction removes free bases
from DNA. Thus, base excision repair protects the cell
from the mutagenic and cytotoxic effects of DNA base
lesions induced by endogenous or exogenous factors.
The ﬁrst enzymatic step of excision repair yields
apurinic/apyrimidinic (AP) sites, DNA lesions of
another type. In addition, AP sites can be generated
spontaneously. Repair of such lesions requires several
biochemical events aimed at restoring the native DNA
structure. Its ﬁnal step involves DNA polymerases and
ligase, which closes single-strand breaks.
DNA glycosylases usually have a low molecular
weight (25–40 kDa), are independent of cofactors, and
have a broad range of substrate speciﬁcities. An essen-
tial property of all DNA glycosylases is generation of
free bases as a product of their reaction with DNA. By
biochemical properties, enzymes of this type are classi-
ﬁed into two groups, monofunctional glycosylases,
which only excise DNA bases, and bifunctional glyco-
sylases/lyases. The latter possess an additional DNA
lyase activity and, producing an AP site, simulta-
neously cleave the phosphodiester bond at its 3' side.
Individual glycosylases greatly vary in the mode of
folding and domain structure. The mechanism of the
biochemical reaction was ﬁrst studied in detail for the
family of uracil-DNA glycosylases, which belong to
the group of monofunctional enzymes.
Uracil ﬁnds its way in DNA via two major mecha-
nisms. First, DNA polymerases may utilize deoxyuri-
dine triphosphate as an analog of dTTP during replica-
tion, producing an adenine–uracil mispair. Second,
cytosine deamination in DNA yields guanine–uracil
pairs, which serve as a source of mutagenesis. It is not
surprising that the proportion of GC AT transitions
in the total mutation spectrum of the
mutant, which is defective in uracil-DNA glycosy-
lase, is dramatically higher than in wild-type cells .
Uracil-DNA glycosylase (Udg) was the ﬁrst to be
discovered among all known glycosylases. All Udg are
monomeric proteins of 19–35 kDa and are highly evo-
lutionarily conserved. Major bacterial Udg removes
uracil from single- or double-stranded DNA and is
encoded by the
gene [2, 3].
Yeast cells were found to contain Udg homologous
to the bacterial enzyme . Strains with mutations of
gene are sensitive to bisulﬁte and nitrous
acid and express a moderate mutator phenotype. The
frequency of spontaneous mutations of the
gene is approximately 20-fold higher than in the
isogenic wild-type strain .
A human homolog of the bacterial and yeast
genes was cloned [6, 7]. In mammals, this gene (
encodes both nuclear and mitochondrial forms of the
enzyme . Surprisingly,
-deﬁcient mice are via-
ble and fertile and show only a slight increase in spon-
taneous mutation rate . This ﬁnding suggests that the
corresponding enzyme plays only a minor role in pro-
Base Excision Repair of DNA: Glycosylases
V. G. Korolev
Konstantinov Institute of Nuclear Physics, Russian Academy of Sciences, Gatchina, Leningrad oblast, 188300 Russia;
fax: (81371)323-03, e-mail: firstname.lastname@example.org
Received October 27, 2004
—The review considers the role of base excision repair in maintaining the constancy of genetic infor-
mation in the cell. The genetic control and biochemical mechanism are described for the ﬁrst stage of base exci-
sion repair, which is catalyzed by speciﬁc enzymes, DNA glycosylases.