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A random Abstract
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Enhancement of human DNA polymerase η activity and fidelity is dependent upon a bipartite interaction with the Werner syndrome protein.
[werner syndrome]
We
have
investigated
the
interaction
between
human
DNA
polymerase
η
(
hpol
η
)
and
the
Werner
syndrome
protein
(
WRN
)
.
Functional
assays
revealed
that
the
WRN
exonuclease
and
RecQ
C-
terminal
(
RQC
)
domains
are
necessary
for
full
stimulation
of
hpol
η-catalyzed
formation
of
correct
base
pairs
.
We
find
that
WRN
does
not
stimulate
hpol
η-catalyzed
formation
of
mispairs
.
Moreover
,
the
exonuclease
activity
of
WRN
prevents
stable
mispair
formation
by
hpol
η
.
These
results
are
consistent
with
a
proofreading
activity
for
WRN
during
single
-nucleotide
additions
.
ATP
hydrolysis
by
WRN
appears
to
attenuate
stimulation
of
hpol
η
.
Pre-steady-
state
kinetic
results
show
that
k
(
pol
)
is
increased
4
-
fold
by
WRN
.
Finally
,
pulldown
assays
reveal
a
bipartite
physical
interaction
between
hpol
η
and
WRN
that
is
mediated
by
the
exonuclease
and
RQC
domains
.
Taken
together
,
these
results
are
consistent
with
alteration
of
the
rate-limiting
step
in
polymerase
catalysis
by
direct
protein-protein
interactions
between
WRN
and
hpol
η
.
In
summary
,
WRN
improves
the
efficiency
and
fidelity
of
hpol
η
to
promote
more
effective
replication
of
DNA
.