MYBL2 maintains stemness and promotes theta-mediated end joining in triple negative breast cancer
Опубликована: Апрель 18, 2025
Abstract
Triple
negative
breast
cancer
(TNBC)
has
a
poor
prognosis
due
to
limited
treatment
options
and
high
metastasis
risk.
Breast
(BC)
stem/progenitor
cells,
also
known
as
tumour
initiating
are
small,
difficult
target
population
within
the
responsible
for
therapy
resistance.
MYBL2
overexpression
is
commonly
linked
but
its
role
in
BC
cells
remains
elusive.
To
determine
of
we
generated
TNBC
cell
lines
with
inducible
downregulation.
Our
findings
reveal
that
elevated
essential
self-renewal,
DNA
repair,
replication
stress
response
these
lowering
impairs
stemness
self-renewal
both
vitro
vivo
.
Accordingly,
our
functional
mechanistic
analyses
indicate
high-MYBL2
exhibit
increased
sensitivity
Polθ
inhibitors
which
lost
upon
downregulation
transcriptional
suppression.
Combining
ATR
further
enhances
this
sensitivity,
ex
vivo.
This
study
thus
identifies
Polθ/ATR
inhibition
synthetic
lethality
strategy
eradicate
underscores
expression
biomarker
patient
stratification
treatment.
Язык: Английский
The Influence of Circadian Rhythms on DNA Damage Repair in Skin Photoaging
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(20), С. 10926 - 10926
Опубликована: Окт. 11, 2024
Circadian
rhythms,
the
internal
timekeeping
systems
governing
physiological
processes,
significantly
influence
skin
health,
particularly
in
response
to
ultraviolet
radiation
(UVR).
Disruptions
circadian
rhythms
can
exacerbate
UVR-induced
damage
and
increase
risk
of
aging
cancer.
This
review
explores
how
affect
various
aspects
physiology
pathology,
with
a
special
focus
on
DNA
repair.
regulation
ensures
optimal
repair
following
damage,
reducing
mutation
accumulation,
enhancing
genomic
stability.
The
control
over
cell
proliferation
apoptosis
further
contributes
regeneration
UVR.
Oxidative
stress
management
is
another
critical
area
where
exert
influence.
Key
genes
like
brain
muscle
ARNT-like
1
(BMAL1)
locomotor
output
cycles
kaput
(CLOCK)
modulate
activity
antioxidant
enzymes
signaling
pathways
protect
cells
from
oxidative
stress.
also
inflammatory
immune
responses
by
modulating
Langerhans
other
skin.
In
summary,
form
complex
defense
network
that
manages
through
precise
repair,
proliferation,
apoptosis,
response,
stress,
hormonal
signaling.
Understanding
these
mechanisms
provides
insights
into
developing
targeted
protection
improving
cancer
prevention.
Язык: Английский
Assessment of DNA Double Strand Break Repair Activity Using High-throughput and Quantitative Luminescence-based Reporter Assays
Journal of Visualized Experiments,
Год журнала:
2024,
Номер
208
Опубликована: Июнь 14, 2024
The
repair
of
DNA
double
strand
breaks
(DSBs)
is
crucial
for
the
maintenance
genome
stability
and
cell
viability.
DSB
(DSBR)
in
cells
mediated
through
several
mechanisms:
homologous
recombination
(HR),
non-homologous
end
joining
(NHEJ),
microhomology-mediated
(MMEJ),
single
annealing
(SSA).
Cellular
assays
are
essential
to
measure
proficiency
modulation
these
pathways
response
various
stimuli.
Here,
we
present
a
suite
extrachromosomal
reporter
that
each
reconstitution
nanoluciferase
gene
by
one
four
major
DSBR
cells.
Upon
transient
transfection
into
interest,
pathway-specific
substrates
can
be
measured
under
24
h
detection
Nanoluciferase
(NanoLuc)
luminescence.
These
robust
quantitative,
sensitive,
titratable,
amenable
high-throughput
screening
format.
properties
provide
broad
applications
research
drug
discovery,
complementing
currently
available
toolkit
cellular
assays.
Язык: Английский
JoVE Video Dataset
Опубликована: Июнь 15, 2024
The
repair
of
DNA
double
strand
breaks
(DSBs)
is
crucial
for
the
maintenance
genome
stability
and
cell
viability.
DSB
(DSBR)
in
cells
mediated
through
several
mechanisms:
homologous
recombination
(HR),
non-homologous
end
joining
(NHEJ),
microhomology-mediated
(MMEJ),
single
annealing
(SSA).
Cellular
assays
are
essential
to
measure
proficiency
modulation
these
pathways
response
various
stimuli.
Here,
we
present
a
suite
extrachromosomal
reporter
that
each
reconstitution
nanoluciferase
gene
by
one
four
major
DSBR
cells.
Upon
transient
transfection
into
interest,
pathway-specific
substrates
can
be
measured
under
24
h
detection
Nanoluciferase
(NanoLuc)
luminescence.
These
robust
quantitative,
sensitive,
titratable,
amenable
high-throughput
screening
format.
properties
provide
broad
applications
research
drug
discovery,
complementing
currently
available
toolkit
cellular
assays.
Язык: Английский
Advancements in Ovarian Cancer Research: Targeting DNA Repair Mechanisms and the Role of DNA Polymerase β Inhibitors
Biosciences Biotechnology Research Asia,
Год журнала:
2024,
Номер
21(4), С. 1439 - 1449
Опубликована: Дек. 20, 2024
ABSTRACT:
Background:
Exposure
to
mutagens
causes
DNA
damage,
which,
if
not
repaired
properly,
can
lead
diseases
like
cancer.
Ovarian
cancer
is
a
major
concern
for
women
globally,
including
in
India,
as
it
often
diagnosed
at
an
advanced
stage,
making
treatment
more
challenging.
Recent
research
implicates
repair
proteins
polymerase
β
(Pol
β)
development,
emphasising
the
need
understand
these
pathways
targeted
therapy.
This
study
uses
bibliometric
analysis
explore
ovarian
and
pathways,
providing
insights
future
treatment.
Materials
Methods:
Data
from
37,539
articles
related
cancer,
β,
inhibitors
were
analysed
Dimensions
database.
Publication
distribution,
national
cooperation,
leading
authors,
trends
examined.
Results:
Variations
publication
distribution
observed
across
journals,
with
notable
contributions
countries
Germany,
Canada,
Netherlands.
Prolific
authors
institutions
identified,
shedding
light
on
global
academic
landscape.
Co-occurrence
revealed
thematic
clusters,
pathophysiology,
risk
associations,
therapeutic
targets,
genomic
research.
Conclusion:
offers
valuable
into
pathways.
It
highlights
importance
of
targeting
mechanisms
therapy
suggests
opportunities
collaboration
personalised
medicine.
Identifying
key
directions
aids
advancing
our
understanding
aiming
improve
patient
outcomes.
Язык: Английский