Replication
protein
A
(RPA)
is
a
heterotrimeric
complex
and
the
main
single-stranded
DNA
(ssDNA)
binding
in
eukaryotes.
RPA
has
key
functions
most
of
DNA-associated
metabolic
pathways
damage
signalling.
Its
high
affinity
for
ssDNA
helps
to
stabilise
structures
prevents
sequence
from
nuclease
attacks.
consists
multiple
DNA-binding
domains
which
are
oligonucleotide/oligosaccharide-binding
(OB)-folds,
responsible
binding,
interactions
with
proteins.
These
RPA-ssDNA
RPA-protein
crucial
replication,
repair,
signalling,
conversation
genetic
information
cells.
Proteins
such
as
ATR
use
locate
regions
Recruitment
nucleases
exchange
factors
sites
double
strand
breaks
also
an
important
function
ensure
effective
recombination
correct
these
lesions.
Due
its
ssDNA,
RPA’s
removal
central
importance
allow
pathway
proceed
processes
against
downstream
established
all
facetted
multi-layered
will
be
discussed
detail
review.
major
player
variety
human
diseases,
discussed.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(1), P. 588 - 588
Published: Jan. 2, 2024
Replication
protein
A
(RPA)
is
a
heterotrimeric
complex
and
the
main
single-stranded
DNA
(ssDNA)-binding
in
eukaryotes.
RPA
has
key
functions
most
of
DNA-associated
metabolic
pathways
damage
signalling.
Its
high
affinity
for
ssDNA
helps
to
stabilise
structures
protect
sequence
from
nuclease
attacks.
consists
multiple
DNA-binding
domains
which
are
oligonucleotide/oligosaccharide-binding
(OB)-folds
that
responsible
binding
interactions
with
proteins.
These
RPA-ssDNA
RPA-protein
crucial
replication,
repair,
signalling,
conservation
genetic
information
cells.
Proteins
such
as
ATR
use
locate
regions
The
recruitment
nucleases
exchange
factors
sites
double-strand
breaks
also
an
important
function
ensure
effective
recombination
correct
these
lesions.
Due
its
ssDNA,
RPA's
removal
central
importance
allow
proceed,
processes
against
downstream
established
all
faceted
multi-layered
well
role
variety
human
diseases
will
be
discussed.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Feb. 11, 2025
Abstract
Loss
of
epigenetic
information
during
physiological
aging
compromises
cellular
identity,
leading
to
de-repression
developmental
genes.
Here,
we
assessed
the
epigenomic
landscape
vulnerable
neurons
in
two
reference
mouse
models
Huntington
neurodegenerative
disease
(HD),
using
cell-type-specific
multi-omics,
including
temporal
analysis
at
three
stages
via
FANS-CUT&Tag.
We
show
accelerated
genes
HD
striatal
neurons,
involving
histone
re-acetylation
and
depletion
H2AK119
ubiquitination
H3K27
trimethylation
marks,
which
are
catalyzed
by
polycomb
repressive
complexes
1
2
(PRC1
PRC2),
respectively.
further
identify
a
PRC1-dependent
subcluster
bivalent
transcription
factors
that
is
re-activated
neurons.
This
mechanism
likely
involves
progressive
paralog
switching
between
PRC1-CBX
genes,
promotes
upregulation
normally
low-expressed
PRC1-CBX2/4/8
isoforms
alongside
down-regulation
predominant
these
cells
(e.g.,
CBX6/7).
Collectively,
our
data
provide
evidence
for
JCI Insight,
Journal Year:
2024,
Volume and Issue:
9(9)
Published: March 21, 2024
Spinocerebellar
ataxia
type
1
(SCA1)
is
a
fatal
neurodegenerative
disease
caused
by
an
expanded
polyglutamine
tract
in
the
widely
expressed
ataxin-1
(ATXN1)
protein.
To
elucidate
anatomical
regions
and
cell
types
that
underlie
mutant
ATXN1-induced
phenotypes,
we
developed
floxed
conditional
knockin
mouse
(f-ATXN1146Q/2Q)
with
Atxn1
coding
exons
replaced
human
ATXN1
encoding
146
glutamines.
f-ATXN1146Q/2Q
mice
manifested
SCA1-like
phenotypes
including
motor
cognitive
deficits,
wasting,
decreased
survival.
Central
nervous
system
(CNS)
contributions
to
were
revealed
using
f-ATXN1146Q/2Q;Nestin-Cre
mice,
showed
improved
rotarod,
open
field,
Barnes
maze
performance
6-12
weeks-of-age.
In
contrast,
striatal
deficits
f-ATXN1146Q/2Q;Rgs9-Cre
lacking
ATXN1146Q/2Q
medium-spiny
neurons
trending
improvement
rotarod
at
30
Surprisingly,
prominent
role
for
muscle
was
f-ATXN1146Q/2Q;ACTA1-Cre
based
on
their
recovery
from
kyphosis
absence
of
pathology.
Collectively,
data
targeted
deletion
allele
demonstrated
CNS
peripheral
highlighted
need
consider
addition
brain
optimal
SCA1
therapeutics.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: April 9, 2025
Abstract
MicroRNAs
(miRNAs)
are
small
non-coding
RNAs
that
play
crucial
roles
in
post-transcriptional
gene
regulation.
Poly(A)
RNA
polymerase
D5
(PAPD5)
catalyzes
the
addition
of
adenosine
to
3′
end
miRNAs.
In
this
study,
we
demonstrate
Yin
Yang
1
protein,
a
transcriptional
repressor
PAPD5,
is
recruited
both
foci
and
protein
aggregates,
resulting
an
upregulation
PAPD5
expression
Huntington’s
disease
(HD).
Additionally,
identify
subset
PAPD5-regulated
miRNAs
with
increased
adenylation
reduced
our
model.
We
focus
on
miR-7-5p
find
its
reduction
causes
activation
TAB2-mediated
TAK1–MKK4–JNK
pro-apoptotic
pathway.
This
pathway
also
activated
induced
pluripotent
stem
cell-derived
striatal
neurons
post-mortem
tissues
isolated
from
HD
patients.
addition,
discover
molecule
inhibitor,
BCH001,
can
mitigate
cell
death
neurodegeneration
models.
study
highlights
importance
PAPD5-mediated
miRNA
dysfunction
pathogenesis
suggests
potential
therapeutic
direction
for
disease.
Aging and Disease,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 1, 2024
N1-methyladenine
(m1A),
a
modification
of
transcripts,
regulates
mRNA
structure
and
translation
efficiency.
In
recent
issue
Nature,
Sun
et
al.
reported
that
m1A
in
CAG
repeat
RNA
contributes
to
expansion-induced
neurodegeneration
Caenorhabditis
elegansDrosophila
through
enhancing
the
ability
endogenous
TDP-43
partition
into
stress
granules
mediated
by
m1A.
The
study
is
especially
important
for
revealing
pathological
function
mechanisms
expansion-related
neurodegenerative
diseases.
Genes,
Journal Year:
2024,
Volume and Issue:
15(2), P. 167 - 167
Published: Jan. 27, 2024
Human
Replication
Protein
A
(RPA)
was
historically
discovered
as
one
of
the
six
components
needed
to
reconstitute
simian
virus
40
DNA
replication
from
purified
components.
RPA
is
now
known
be
involved
in
all
metabolism
pathways
that
involve
single-stranded
(ssDNA).
Heterotrimeric
comprises
several
domains
connected
by
flexible
linkers
and
heavily
regulated
post-translational
modifications
(PTMs).
The
structure
has
been
challenging
obtain.
Various
structural
methods
have
applied,
but
a
complete
understanding
RPA's
structure,
its
function,
how
it
PTMs
yet
obtained.
This
review
will
summarize
recent
literature
concerning
phosphorylated
cell
cycle,
analysis
RPA,
protein
interactions
involving
regulate
activity
complex
formation
double-strand
break
repair.
There
are
many
holes
our
this
research
area.
We
conclude
with
perspectives
for
future
on
control
repair
cycle.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(14), P. 7906 - 7906
Published: July 19, 2024
Neurons
in
the
brain
are
continuously
exposed
to
various
sources
of
DNA
damage.
Although
mechanisms
damage
repair
mitotic
cells
have
been
extensively
characterized,
pathways
post-mitotic
neurons
still
largely
elusive.
Moreover,
inaccurate
can
result
deleterious
mutations,
including
deletions,
insertions,
and
chromosomal
translocations,
ultimately
compromising
genomic
stability.
Since
terminally
differentiated
cells,
they
cannot
employ
homologous
recombination
(HR)
for
double-strand
break
(DSB)
repair,
suggesting
existence
neuron-specific
mechanisms.
Our
research
has
centered
on
microtubule-associated
protein
tau
(MAPT),
a
crucial
pathological
implicated
neurodegenerative
diseases,
its
interplay
with
neurons'
response
(DDR).
This
review
aims
provide
an
updated
synthesis
current
understanding
complex
between
DDR
cytoskeletal
proteins
neurons,
particular
focus
role
disorders.
