Journal of Translational Genetics and Genomics,
Год журнала:
2023,
Номер
unknown
Опубликована: Янв. 1, 2023
Maintenance
of
genome
integrity
is
essential
for
cellular
survival.
There
are
mechanisms
utilized
by
the
cells
to
sense
and
respond
assaults
on
genomic
DNA.
These
conserved
across
all
domains
life
collectively
called
DNA
damage
response
pathways.
However,
eukaryotic
also
have
extrachromosomal
in
mitochondria
(mtDNA),
which
indispensable
mitochondrial
function,
hence
cell
Indeed,
impaired
activity
arising
due
mutations
mtDNA
has
been
found
be
associated
with
many
human
pathologies.
Despite
its
importance,
our
understanding
how
ensure
limited.
Since
do
not
encode
machinery
required
maintenance
their
own
genomes,
they
depend
nucleus
replication,
transcription,
repair
processes.
This
adds
a
layer
complexity
requirement
organelle
crosstalk
coordination
damage.
review
summarizes
recent
findings
that
provide
new
insights
into
involved
quality
control,
acting
at
level
or
discusses
few
avenues
research
towards
comprehensive
“mtDNA
response”.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 26, 2024
The
molecular
pathogenesis
of
diabetes
is
multifactorial,
involving
genetic
predisposition
and
environmental
factors
that
are
not
yet
fully
understood.
However,
pancreatic
β-cell
failure
remains
among
the
primary
reasons
underlying
progression
type-2
(T2D)
making
targeting
dysfunction
an
attractive
pathway
for
treatment.
To
identify
contributors
to
dysfunction,
we
investigated
single-cell
gene
expression
changes
in
β-cells
from
healthy
(C57BL/6J)
diabetic
(NZO/HlLtJ)
mice
fed
with
normal
or
high-fat,
high-sugar
diet
(HFHS).
Our
study
presents
innovative
integration
causal
network
perturbation
assessment
(ssNPA)
framework
meta-cell
transcriptome
analysis
explore
underpinnings
(T2D).
By
generating
a
reference
Nucleic Acids Research,
Год журнала:
2024,
Номер
52(20), С. e97 - e97
Опубликована: Сен. 10, 2024
Here,
we
employed
a
fluorescence-based
single
molecule
method
called
nuclease-induced
stepwise
photodropping
(NISP)
to
measure
in
real
time
the
DNA
degradation
mediated
by
mitochondrial
genome
maintenance
exonuclease
1
(MGME1),
bidirectional
single-stranded
(ssDNA)-specific
exonuclease.
The
detects
decrease
fluorescence
signals
from
Cy3
fluorophores
labeled
on
an
immobilized
substrate.
Using
NISP,
successfully
determined
rates
of
6.3
±
0.4
and
2.0
0.1
nucleotides
(nt)
s-1
for
MGME1
5'-to-3'
3'-to-5'
directions,
respectively.
These
results
provide
direct
evidence
stronger
5'
directionality
MGME1,
consistent
with
its
established
role
maintenance.
Importantly,
when
NISP
investigate
mung
bean
nuclease,
ss-specific
endonuclease,
observed
markedly
different
pattern,
suggesting
distributive
cleavage
activity
enzyme.
Furthermore,
applied
determine
ssDNA
behavior
double-stranded-specific
exonuclease,
λ
findings
underscore
capability
accurately
reliably
both
exo-
endonucleases.
demonstrate
as
powerful
tool
investigating
nucleases
at
single-molecule
level.
Journal of Translational Genetics and Genomics,
Год журнала:
2023,
Номер
unknown
Опубликована: Янв. 1, 2023
Maintenance
of
genome
integrity
is
essential
for
cellular
survival.
There
are
mechanisms
utilized
by
the
cells
to
sense
and
respond
assaults
on
genomic
DNA.
These
conserved
across
all
domains
life
collectively
called
DNA
damage
response
pathways.
However,
eukaryotic
also
have
extrachromosomal
in
mitochondria
(mtDNA),
which
indispensable
mitochondrial
function,
hence
cell
Indeed,
impaired
activity
arising
due
mutations
mtDNA
has
been
found
be
associated
with
many
human
pathologies.
Despite
its
importance,
our
understanding
how
ensure
limited.
Since
do
not
encode
machinery
required
maintenance
their
own
genomes,
they
depend
nucleus
replication,
transcription,
repair
processes.
This
adds
a
layer
complexity
requirement
organelle
crosstalk
coordination
damage.
review
summarizes
recent
findings
that
provide
new
insights
into
involved
quality
control,
acting
at
level
or
discusses
few
avenues
research
towards
comprehensive
“mtDNA
response”.
