bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 8, 2023
SUMMARY
Phase
separation
forms
membraneless
compartments
in
the
nuclei,
including
by
establishing
heterochromatin
“domains”
and
repair
foci.
Pericentromeric
mostly
comprises
repeated
sequences
prone
to
aberrant
recombination,
“safe”
homologous
recombination
(HR)
of
these
requires
movement
sites
nuclear
periphery
before
Rad51
recruitment
strand
invasion.
How
this
mobilization
initiates
is
unknown,
contribution
phase
dynamics
unclear.
Here,
we
show
that
Nup98
nucleoporin
recruited
heterochromatic
relocalization
through
Sec13
or
Nup88
nucleoporins,
downstream
from
Smc5/6
complex
SUMOylation.
Remarkably,
properties
are
required
sufficient
mobilize
exclude
Rad51,
thus
preventing
while
promoting
HR
repair.
Disrupting
pathway
results
defects
widespread
chromosome
rearrangements,
revealing
a
novel
“off-pore”
role
for
nucleoporins
genome
integrity
multicellular
eukaryote.
Highlights
recruit
DSBs
Nup88,
promote
focus
‘off-pore’
excludes
inside
domain
exclusion
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Фев. 12, 2024
Abstract
The
phenomenon
of
phase
separation
is
quite
common
in
cells,
and
it
involved
multiple
processes
life
activities.
However,
the
current
research
on
correlation
between
protein
modifications
interference
with
tendency
has
some
limitations.
Here
we
focus
several
post-translational
proteins,
including
phosphorylation
modification
at
sites,
methylation
modification,
acetylation
ubiquitination
SUMOylation
etc.,
which
regulate
formation
stability
structure
through
multivalent
interactions.
This
regulatory
role
closely
related
to
development
neurodegenerative
diseases,
tumors,
viral
infections,
other
also
plays
essential
functions
environmental
stress,
DNA
damage
repair,
transcriptional
regulation,
signal
transduction,
cell
homeostasis
living
organisms,
provides
an
idea
explore
interaction
novel
separation.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Сен. 22, 2023
The
SUMO
protease
SENP6
maintains
genomic
stability,
but
mechanistic
understanding
of
this
process
remains
limited.
We
find
that
deconjugates
SUMO2/3
polymers
on
a
group
DNA
damage
response
proteins,
including
BRCA1-BARD1,
53BP1,
BLM
and
ERCC1-XPF.
these
proteins
in
hypo-SUMOylated
state
under
unstressed
conditions
counteracts
their
polySUMOylation
after
hydroxyurea-induced
stress.
Co-depletion
RNF4
leads
to
further
increase
SUMOylation
BRCA1,
BARD1
BLM,
suggesting
antagonizes
targeting
by
RNF4.
Functionally,
depletion
results
uncoordinated
recruitment
persistence
at
UVA
laser
ionizing
radiation
induced
sites.
Additionally,
accumulate
nuclear
bodies,
PML-independent
manner
driven
multivalent
SUMO-SIM
interactions.
These
data
illustrate
coordinated
regulation
SUMOylated
SENP6,
governing
timely
localization
sites
condensation
state.
DNA repair,
Год журнала:
2023,
Номер
128, С. 103524 - 103524
Опубликована: Июнь 10, 2023
Cells
have
evolved
an
arsenal
of
molecular
mechanisms
to
respond
continuous
alterations
in
the
primary
structure
DNA.
At
cellular
level,
DNA
damage
response
proteins
accumulate
at
sites
and
organize
into
nuclear
foci.
As
recounted
by
Errol
Friedberg,
pioneering
work
on
repair
1930
s
was
stimulated
collaborations
between
physicists
geneticists.
In
recent
years,
introduction
ideas
from
physics
self-organizing
compartments
has
taken
field
cell
biology
storm.
Percolation
phase
separation
theories
are
increasingly
used
model
self-assembly
compartments,
called
biomolecular
condensates,
that
selectively
concentrate
molecules
without
a
surrounding
membrane.
this
review,
we
discuss
these
concepts
context
response.
We
how
studies
foci
as
condensates
can
link
with
physiological
functions,
provide
new
insights
regulatory
mechanisms,
open
perspectives
for
targeting
responses
therapeutic
purposes.
Molecular Cell,
Год журнала:
2024,
Номер
84(4), С. 640 - 658.e10
Опубликована: Янв. 23, 2024
The
Bloom
syndrome
helicase
BLM
interacts
with
topoisomerase
IIIα
(TOP3A),
RMI1,
and
RMI2
to
form
the
BTR
complex,
which
dissolves
double
Holliday
junctions
DNA
replication
intermediates
promote
sister
chromatid
disjunction
before
cell
division.
In
its
absence,
structure-specific
nucleases
like
SMX
complex
(comprising
SLX1-SLX4,
MUS81-EME1,
XPF-ERCC1)
can
cleave
joint
molecules
instead,
but
cells
deficient
in
both
are
not
viable.
Here,
we
identify
a
negative
genetic
interaction
between
loss
deficiency
BRCA1-BARD1
tumor
suppressor
complex.
We
show
that
this
is
due
previously
overlooked
role
for
BARD1
recruiting
SLX4
resolve
left
unprocessed
by
preceding
interphase.
Consequently,
defective
accumulate
catastrophic
levels
of
chromosome
breakage
micronucleation,
leading
death.
Thus,
reveal
mechanistic
insights
into
recruitment
lesions,
potential
clinical
implications
treating
BRCA1-deficient
tumors.
Biochemical Society Transactions,
Год журнала:
2024,
Номер
52(2), С. 773 - 792
Опубликована: Апрель 17, 2024
The
preservation
of
genome
integrity
requires
specialised
DNA
damage
repair
(DDR)
signalling
pathways
to
respond
each
type
damage.
A
key
feature
DDR
is
the
integration
numerous
post-translational
modification
signals
with
factors.
These
modifications
influence
factor
recruitment
damaged
DNA,
activity,
protein-protein
interactions,
and
ultimately
eviction
enable
access
for
subsequent
factors
or
termination
signalling.
SUMO1-3
(small
ubiquitin-like
modifier
1-3)
conjugation
has
gained
much
recent
attention.
SUMO-modified
proteome
enriched
Here
we
provide
a
snapshot
our
current
understanding
how
SUMO
impacts
major
in
mammalian
cells.
We
highlight
repeating
themes
used
throughout
including
assembly
protein
complexes,
competition
ubiquitin
promote
stability
ubiquitin-dependent
degradation
extraction
SUMOylated
As
'addiction'
cancer
cells
protective
genomic
integrity,
targeting
components
machinery
potentiate
damaging
therapy
exacerbate
existing
defects
promising
area
study.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Фев. 21, 2024
Abstract
Phase
separation
is
a
cellular
phenomenon
where
macromolecules
aggregate
or
segregate,
giving
rise
to
biomolecular
condensates
resembling
"droplets"
and
forming
distinct,
membrane-free
compartments.
This
process
pervasive
in
biological
cells,
contributing
various
essential
functions.
However,
when
phase
goes
awry,
leading
abnormal
molecular
aggregation,
it
can
become
driving
factor
the
development
of
diseases,
including
tumor.
Recent
investigations
have
unveiled
intricate
connection
between
dysregulated
tumor
pathogenesis,
highlighting
its
potential
as
novel
therapeutic
target.
article
provides
an
overview
recent
research,
with
particular
emphasis
on
role
tumor,
implications,
outlines
avenues
for
further
exploration
this
intriguing
field.
Journal of Molecular Biology,
Год журнала:
2025,
Номер
unknown, С. 168951 - 168951
Опубликована: Янв. 1, 2025
Alternative
Lengthening
of
Telomeres
(ALT)
pathway
is
a
telomerase-independent
mechanism
that
utilizes
homology-directed
repair
(HDR)
to
sustain
telomere
length
in
specific
cancers.
Biomolecular
condensates,
such
as
ALT-associated
promyelocytic
leukemia
nuclear
bodies
(APBs),
have
emerged
critical
players
the
ALT
pathway,
supporting
maintenance
ALT-positive
cells.
These
condensates
bring
together
DNA
proteins,
telomeric
repeats,
and
other
regulatory
elements.
By
regulating
replication
stress
promoting
synthesis,
create
an
environment
conducive
HDR-based
extension.
This
review
explores
recent
advancements
ALT,
focusing
on
understanding
role
biomolecular
how
they
impact
dynamics
stability.
