Deciphering the dark side of histone ADP-ribosylation: what structural features of damaged nucleosome regulate the activities of PARP1 and PARP2
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
ABSTRACT
Poly(ADP-ribose)
polymerases
are
critical
enzymes
contributing
to
regulation
of
numerous
cellular
processes,
including
DNA
repair.
Within
the
PARP
family,
PARP1
and
PARP2
primarily
facilitate
PARylation
in
nucleus,
particularly
responding
genotoxic
stress.
The
activity
PARPs
is
influenced
by
nature
damage
multiple
protein
partners,
with
HPF1
being
important
one.
Forming
a
joint
active
site
(PARP2),
contributes
histone
following
chromatin
remodelling
during
stress
events.
This
study
elucidates
interrelation
between
presence
location
one-nucleotide
gap
within
nucleosome
core
particle
(NCP)
activities
automodification
heteromodification
histones.
Utilizing
combination
classical
biochemical
methods
fluorescence-based
technique
single-molecule
mass
photometry
approach,
we
have
shown
that
NCP
architecture
impacts
efficiency
pattern
ADP-ribosylation
binding
histones-associated
damaged
more
significantly
for
than
PARP1.
Analysis
based
on
existing
studies
HPF1-dependent
ADP-ribosylome
structural
dynamics
allows
suggest
conformational
flexibility
tails
modulated
post-translational
modifications
crucial
delineating
distinct
roles
responses.
GRAPHICAL
Язык: Английский
HPF1 Regulates Pol β Efficiency in Nucleosomes via the Modulation of Total Poly(ADP-Ribose) Synthesis
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(5), С. 1794 - 1794
Опубликована: Фев. 20, 2025
The
maintenance
of
genome
stability
and
the
prevention
genotoxic
damage
to
DNA
require
immediate
repair.
In
cell,
repair
process
is
usually
preceded
by
a
release
from
complexes
with
chromatin
proteins
accompanied
nucleosome
sliding,
relaxing
or
disassembly.
Base
excision
(BER)
corrects
most
common
lesions,
which
does
not
disturb
helix
dramatically.
Notably,
small
lesions
can
be
repaired
in
without
global
decompaction.
One
regulatory
mechanisms
poly(ADP-ribosyl)ation,
leading
relaxation
nucleosome.
our
work,
we
demonstrated
that
recently
discovered
protein,
HPF1,
modulate
efficiency
one
key
BER
stages-DNA
synthesis-via
regulation
total
poly(ADP-ribosyl)ation.
Accordingly,
investigated
both
short-patch
long-patch
synthesis
catalyzed
polymerase
β
(pol
β;
main
BER)
showed
HPF1's
influence
on
poly(ADP-ribosyl)ation
PARP1
especially
PARP2
results
more
efficient
case
pathway
nucleosomes.
Additionally,
HPF1-dependent
was
found
positively
regulate
BER.
Язык: Английский