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RECQL5 plays co-operative and complementary roles with WRN syndrome helicase.
[werner syndrome]
Humans
have
five
RecQ
helicases
,
whereas
simpler
organisms
have
only
one
.
Little
is
known
about
whether
and
how
these
RecQ
helicases
co
-operate
and
/
or
complement
each
other
in
response
to
cellular
stress
.
Here
we
show
that
RECQL
5
associates
longer
at
laser-induced
DNA
double
-strand
breaks
in
the
absence
of
Werner
syndrome
(
WRN
)
protein
,
and
that
it
interacts
physically
and
functionally
with
WRN
both
in
vivo
and
in
vitro
.
RECQL
5
co
-operates
with
WRN
on
synthetic
stalled
replication
fork-like
structures
and
stimulates
its
helicase
activity
on
DNA
fork
duplexes
.
Both
RECQL
5
and
WRN
re
-localize
from
the
nucleolus
into
the
nucleus
after
replicative
stress
and
significantly
associate
with
each
other
during
S-
phase
.
Further
,
we
show
that
RECQL
5
is
essential
for
cell
survival
in
the
absence
of
WRN
.
Loss
of
both
RECQL
5
and
WRN
severely
compromises
DNA
replication
,
accumulates
genomic
instability
and
ultimately
leads
to
cell
death
.
Collectively
,
our
results
indicate
that
RECQL
5
plays
both
co
-operative
and
complementary
roles
with
WRN
.
This
is
an
early
demonstration
of
a
significant
functional
interplay
and
a
novel
synthetic
lethal
interaction
among
the
human
RecQ
helicases
.
Diseases
Validation
Diseases presenting
"significant functional interplay"
symptom
werner syndrome
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