DNA
Repair:
Base
Excision
from
Bacteria
to
Man
Johan
H.
van
de
Sande
Department
of
Biochemistry
and
Molecular
Biology
Faculty
of
Medicine
University
of
Calgary
Calgary,
Alberta,
Canada
DNA
is
subject
to
a
number
of
potentially
mutagenic
events
resulting
from
errors
in
replication,
spontaneous
chemical
reactions
and
exposure
to
a
number
of
environmental
agents.
Cells
have
evolved
an
effective
repair
mechanism
to
deal
with
DNA
modification
and
DNA
damage
in
order
to
maintain
the
integrity
of
the
genome.
Repair
and
maintenance
of
DNA
is
achieved
through
the
utilisation
of
five
characterised
repair
pathways;
direct
damage
reversal,
double-strand
break
repair,
mismatch-directed
repair,
nucleotide
excision
repair
(NER)
and
base
excision
repair
(BER).
Of
the
various
insults
to
DNA,
the
lesions
repaired
by
the
base
excision
repair
pathway
are
the
most
prevalent.
In
contrast
to
repair
pathways
such
as
NER
which
utilise
a
single
enzyme
complex
to
repair
a
variety
of
DNA
lesions,
the
BER
pathway
relies
on
a
number
of
enzymes
specific
for
each
damaged
or
inappropriate
base
encountered
in
the
cell.
Base
excision
repair
is
initiated
through
the
recognition
of
a
damaged
or
inappropriate
base
by
one
of
a
number
of
lesion-specific
DNA
glycosylases.
One
of
these
ubiquitous
DNA
repair
glycosylases
is
Uracil
DNA
Glycosylase
(UDG),
the
product
of
the
ung
gene.
Uracil
in
DNA
results
from
either
the
direct
incorporation
of
deoxyuridine
instead
of
thymine
during
DNA
synthesis
or
from
the
deamination
of
cytosine.
If
left
uncorrected,
the
incorporation
of
uracil
in
DNA
can
result
in
guanine
to
adenine
transitions.
A
major
research
focus
is
the
structural,
functional
and
biological
characterisation
of
Uracil
DNA
Glycosylase
from
bacteria
and
mammals.
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