International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(21), С. 12815 - 12815
Опубликована: Окт. 24, 2022
ATP-dependent
chromatin-remodeling
complexes
can
reorganize
and
remodel
chromatin
thereby
act
as
important
regulator
in
various
cellular
processes.
Based
on
considerable
studies
over
the
past
two
decades,
it
has
been
confirmed
that
abnormal
function
of
remodeling
plays
a
pivotal
role
genome
reprogramming
for
oncogenesis
cancer
development
and/or
resistance
to
therapy.
Recently,
exciting
progress
made
identification
genetic
alteration
genes
encoding
associated
with
tumorigenesis,
well
our
understanding
mechanisms
biology.
Here,
we
present
preclinical
evidence
explaining
signaling
involving
misregulation-induced
processes,
including
DNA
damage
signaling,
metastasis,
angiogenesis,
immune
etc.
However,
even
though
cumulative
this
field
provides
promising
emerging
molecules
therapeutic
explorations
cancer,
more
research
is
needed
assess
clinical
roles
these
targets.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Дек. 16, 2021
Transcription
poses
a
threat
to
genomic
stability
through
the
formation
of
R-loops
that
can
obstruct
progression
replication
forks.
are
three-stranded
nucleic
acid
structures
formed
by
an
RNA-DNA
hybrid
with
displaced
non-template
DNA
strand.
We
developed
Proximity
Proteomics
map
R-loop
proximal
proteome
human
cells
using
quantitative
mass
spectrometry.
implicate
different
cellular
proteins
in
regulation
and
identify
role
tumor
suppressor
DDX41
opposing
double
strand
break
accumulation
promoters.
is
enriched
promoter
regions
vivo,
unwind
hybrids
vitro.
upon
loss
accompanied
stress,
increase
breaks
transcriptome
changes
associated
inflammatory
response.
Germline
loss-of-function
mutations
lead
predisposition
acute
myeloid
leukemia
adulthood.
propose
instability-associated
response
may
contribute
development
familial
AML
mutated
DDX41.
Cell Reports,
Год журнала:
2024,
Номер
43(2), С. 113779 - 113779
Опубликована: Фев. 1, 2024
R-loops
are
three-stranded
structures
that
can
pose
threats
to
genome
stability.
RNase
H1
precisely
recognizes
drive
their
resolution
within
the
genome,
but
underlying
mechanism
is
unclear.
Here,
we
report
ARID1A
with
high
affinity
in
an
ATM-dependent
manner.
recruits
METTL3
and
METTL14
R-loop,
leading
m6A
methylation
of
R-loop
RNA.
This
modification
facilitates
recruitment
driving
its
promoting
DNA
end
resection
at
DSBs,
thereby
ensuring
Depletion
ARID1A,
METTL3,
or
leads
accumulation
reduced
cell
survival
upon
exposure
cytotoxic
agents.
Therefore,
function
a
coordinated,
temporal
order
DSB
sites
recruit
ensure
efficient
resolution.
Given
association
levels
resistance
genotoxic
therapies
patients,
these
findings
open
avenues
for
exploring
potential
therapeutic
strategies
cancers
abnormalities.
Journal of Cellular and Molecular Medicine,
Год журнала:
2025,
Номер
29(1)
Опубликована: Янв. 1, 2025
ABSTRACT
Bladder
cancer
originates
from
bladder
tissues
and
is
the
ninth
most
common
type
of
worldwide.
The
SWI/SNF
(SWItch/sucrose
non‐
fermentable)
complex
plays
a
crucial
role
in
regulating
various
biological
processes,
such
as
cell
cycle
control,
DNA
damage
repair
transcription
regulation.
purpose
this
article
to
examine
functional
studies
cancer,
highlighting
new
pathways
for
creating
personalised
treatment
approaches
patients
with
mutations
complex.
By
acquiring
comprehensive
understanding
mechanisms
we
can
offer
more
precise
effective
solutions
treat
disease.
Journal of Biomedical Science,
Год журнала:
2022,
Номер
29(1)
Опубликована: Сен. 19, 2022
Abstract
Chromatin
remodeling
is
an
essential
cellular
process
for
organizing
chromatin
structure
into
either
open
or
close
configuration
at
specific
locations
by
orchestrating
and
modifying
histone
complexes.
This
task
responsible
fundamental
cell
physiology
including
transcription,
DNA
replication,
methylation,
damage
repair.
Aberrations
in
this
activity
have
emerged
as
epigenomic
mechanisms
cancer
development
that
increase
tumor
clonal
fitness
adaptability
amidst
various
selection
pressures.
Inactivating
mutations
AT-rich
interaction
domain
1A
(
ARID1A
),
a
gene
encoding
large
nuclear
protein
member
belonging
to
the
SWI/SNF
complex,
result
its
loss
of
expression.
most
commonly
mutated
remodeler
gene,
exhibiting
highest
mutation
frequency
endometrium-related
uterine
ovarian
carcinomas.
As
suppressor
regulating
cycle,
facilitating
repair,
controlling
expression
genes
are
maintaining
differentiation
homeostasis
non-transformed
cells.
Thus,
deficiency
due
somatic
propels
progression
dissemination.
The
recent
success
PARP
inhibitors
treating
homologous
recombination
repair-deficient
tumors
has
engendered
keen
interest
developing
synthetic
lethality-based
therapeutic
strategies
-mutated
neoplasms.
In
review,
we
summarize
advances
understanding
biology
development,
with
special
emphasis
on
roles
We
also
discuss
harness
lethal
future
therapeutics
against
cancers.
Cell Reports,
Год журнала:
2022,
Номер
38(10), С. 110411 - 110411
Опубликована: Март 1, 2022
Epstein-Barr
virus
(EBV)
persistently
infects
people
worldwide.
Delivery
of
∼170-kb
EBV
genomes
to
nuclei
and
use
nuclear
membrane-less
replication
compartments
(RCs)
for
their
lytic
cycle
amplification
necessitate
evasion
intrinsic
antiviral
responses.
Proteomics
analysis
indicates
that,
upon
B
cell
infection
or
reactivation,
depletes
the
cohesin
SMC5/6,
which
has
major
roles
in
chromosome
maintenance
DNA
damage
repair.
The
tegument
protein
BNRF1
targets
SMC5/6
complexes
by
a
ubiquitin
proteasome
pathway
dependent
on
calpain
proteolysis
Cullin-7.
In
absence
BNRF1,
associates
with
R-loop
structures,
including
at
viral
origin
replication,
interferes
RC
formation
encapsidation.
CRISPR
identifies
restriction
components
involved
entrapment
SUMOylation.
Our
study
highlights
as
an
immune
sensor
factor
human
herpesvirus
implications
pathogenesis
EBV-associated
cancers.
