Transcription: friend or foe of genome stability
FEBS Letters,
Journal Year:
2025,
Volume and Issue:
599(2), P. 143 - 146
Published: Jan. 1, 2025
Language: Английский
Mechanisms underlining R-loop biology and implications for human disease
Junzhe Liu,
No information about this author
Fengze Li,
No information about this author
Yulong Cao
No information about this author
et al.
Frontiers in Cell and Developmental Biology,
Journal Year:
2025,
Volume and Issue:
13
Published: Feb. 21, 2025
R-loops
are
three-stranded
non-canonical
nucleic
acid
structures
composed
of
nascent
RNA
hybridized
with
the
template
DNA
strand,
leaving
non-template
strand
displaced.
These
play
crucial
roles
in
regulating
gene
expression,
replication,
and
transcription
processes.
However,
have
also
been
increasingly
described
as
highly
deleterious,
causing
genomic
instability
damage.
To
maintain
at
a
relatively
safe
level,
complex
regulatory
mechanisms
exist
to
prevent
their
excessive
formation.
The
growing
understanding
R-loop
functions
has
provided
valuable
insights
into
structure
potential
clinical
applications.
Emerging
research
indicates
that
contribute
pathogenesis
various
disorders,
including
neurodegenerative,
immune-related,
neoplastic
diseases.
This
review
summarizes
metabolism
its
significance
etiology
associated
disorders.
By
elucidating
governing
R-loops,
we
aim
establish
theoretical
foundation
for
disease
exploring
novel
therapeutic
strategies
targeting
these
hybrid
structures.
Language: Английский
Epitranscriptome in action: RNA modifications in the DNA damage response
Molecular Cell,
Journal Year:
2024,
Volume and Issue:
84(19), P. 3610 - 3626
Published: Oct. 1, 2024
Language: Английский
Cross-regulation of RNA methylation modifications and R-loops: from molecular mechanisms to clinical implications
Cellular and Molecular Life Sciences,
Journal Year:
2024,
Volume and Issue:
82(1)
Published: Dec. 10, 2024
R-loops,
RNA–DNA
hybrid
structures,
are
integral
to
key
cellular
processes
such
as
transcriptional
regulation,
DNA
replication,
and
repair.
However,
aberrant
accumulation
of
R-loops
can
compromise
genomic
integrity,
leading
the
development
various
diseases.
Emerging
evidence
underscores
pivotal
role
RNA
methylation
modifications,
particularly
N6-methyladenosine
(m6A)
5-methylcytosine
(m5C),
in
orchestrating
formation,
resolution,
stabilization
R-loops.
These
modifications
dynamically
regulate
R-loop
metabolism,
exerting
bidirectional
control
by
either
facilitating
or
resolving
structures
during
gene
expression
regulation
damage
Dysregulation
resultant
imbalance
homeostasis
closely
linked
pathogenesis
diseases
cancer
neurodegenerative
disorders.
Thus,
deciphering
cross-talk
between
is
essential
for
understanding
mechanisms
underlying
stability
identifying
novel
therapeutic
targets.
This
review
provides
a
comprehensive
analysis
dynamics,
examines
their
physiological
pathological
implications,
proposes
future
directions
intervention
targeting
these
processes.
Language: Английский
RNA Polymerase II is a Polar Roadblock to a Progressing DNA Fork
Teresa Kay,
No information about this author
James T. Inman,
No information about this author
Lucyna Lubkowska
No information about this author
et al.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 13, 2024
DNA
replication
and
transcription
occur
simultaneously
on
the
same
template,
leading
to
inevitable
conflicts
between
replisome
RNA
polymerase.
These
can
stall
fork
threaten
genome
stability.
Although
numerous
studies
show
that
head-on
are
more
detrimental
prone
promoting
R-loop
formation
than
co-directional
conflicts,
fundamental
cause
for
polymerase
roadblock
polarity
remains
unclear,
structure
of
these
R-loops
is
speculative.
In
this
work,
we
use
a
simple
model
system
address
complex
question
by
examining
Pol
II
advanced
via
mechanical
unzipping
mimic
progression.
We
found
binds
stably
resist
removal
in
configuration,
even
with
minimal
transcript
size,
demonstrating
has
an
inherent
polarity.
However,
elongating
long
becomes
potent
persistent
while
retaining
polarity,
RNA-DNA
hybrid
mediates
enhancement.
Surprisingly,
discovered
when
collides
backtracked,
form
lagging
strand
front
II,
creating
topological
lock
traps
at
fork.
TFIIS
facilitates
severing
connection
hybrid.
further
demonstrate
prime
T7
still
bound
DNA.
Our
findings
capture
basal
properties
interactions
fork,
revealing
significant
implications
transcription-replication
conflicts.
Language: Английский
Kinetic Features of Degradation of R-Loops by RNase H1 from Escherichia coli
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(22), P. 12263 - 12263
Published: Nov. 15, 2024
R-loops
can
act
as
replication
fork
barriers,
creating
transcription-replication
collisions
and
inducing
stress
by
arresting
DNA
synthesis,
thereby
possibly
causing
aberrant
processing
the
formation
of
strand
breaks.
RNase
H1
(RH1)
is
one
enzymes
that
participates
in
R-loop
degradation
cleaving
RNA
within
a
hybrid
RNA-DNA
duplex.
In
this
study,
kinetic
features
interaction
RH1
from
Language: Английский