The Plant Journal,
Год журнала:
2024,
Номер
120(5), С. 1735 - 1750
Опубликована: Ноя. 21, 2024
SUMMARY
Heat
is
a
critical
environmental
stress
for
plant
survival.
One
of
its
harmful
effects
on
the
cells
disruption
genome
integrity.
However,
mechanisms
by
which
plants
cope
with
heat‐induced
DNA
damage
remain
largely
unknown.
RMI1,
component
RTR
(RECQ4‐TOP3α‐RMI1)
complex,
plays
pivotal
role
in
maintaining
stability.
In
this
study,
we
identified
target
gene
RMI1
characterizing
high‐temperature‐sensitive
mutant.
The
growth
and
development
rmi1‐1
seedlings
carrying
non‐frameshift
mutation
were
hindered
at
38°C.
Abnormal
mitotic
chromosome
behaviours
ultimately
led
to
cell
death
root
tips.
Additionally,
presence
fragments
during
anaphase
I
caused
pollen
abortion
sterility
plants.
Yeast
two‐hybrid
assays
revealed
that
interactions
between
RMI1‐1
RECQ4
or
TOP3α
weakened
increasing
temperature
entirely
ceased
36°C.
contrast,
functional
maintained
under
same
conditions.
These
results
indicate
disrupts
formation
complex
high
temperatures,
leading
defects
repair
increased
sensitivity
heat
stress.
embryos
rmi1‐cr2
mutant
frameshift
exhibited
complete
lethality.
addition,
overexpression
enhanced
tolerance
rice.
findings
provide
insights
into
molecular
responds
temperatures
stability
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 29, 2024
Abstract
Genome
rearrangement
is
a
hallmark
of
cancer
and
ageing.
DNA
double-strand
breaks
(DSBs)
are
highly
toxic
lesions
that
can
generate
genome
rearrangements.
Several
pathways
compete
for
DSB
repair,
selection
the
appropriate
repair
process
decisive
genetic
stability.
act
according
to
two
steps:
1-the
choice
between
nonhomologous
end-joining
(NHEJ)
versus
resection
ends,
generating
single-stranded
(ssDNA);
2-on
ssDNA,
homologous
recombination
(HR)
sub-processes.
Here
we
show
53BP1,
which
plays
prime
role
at
first
step
by
protecting
against
fostering
NHEJ,
physically
interacts
with
catalytic
subunits
cAMP
dependant
protein
kinase
A
(PKAcs).
PKA
favors
recruitment
53BP1
damages
sites,
consistently,
prevents
resection,
favoring
NHEJ.
Inhibition
stimulated
coherently
reduces
Reversely,
activation
8-Bromo-cAMP
stimulate
NHEJ
HR.
These
data
open
new
avenues
potential
anticancer
strategies.
More
generally,
they
underline
high
complexity
regulation
identifying
as
novel
actor
damage
response,
acting
process,
might
be
essential
integrity
maintenance.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 30, 2024
ABSTRACT
The
identification
and
control
of
high-risk
host
cell
proteins
(HCPs)
in
biotherapeutics
development
is
crucial
for
ensuring
product
quality
shelf
life.
Specifically,
HCPs
with
hydrolase
activity
can
cause
degradation
excipient
polysorbates
(PS),
leading
to
a
decrease
the
life
drug
product.
In
this
study,
we
systematically
optimized
every
step
an
activity-based
protein
profiling
(ABPP)
workflow
identify
trace
amounts
active
polysorbate-degradative
enzymes
(PSDEs)
process
intermediates.
Evaluation
various
parameters
during
sample
preparation
pinpointed
optimal
pH
level
fluorophosphonate
(FP)-biotin
concentration.
Moreover,
combined
use
short
liquid
chromatography
gradient
fast-scanning
Parallel
Accumulation
Serial
Fragmentation
(PASEF)
methodology
increased
throughput
without
compromising
coverage.
Tuning
Trapped
Ion
Mobility
Spectrometry
(TIMS)
further
enhanced
sensitivity.
addition,
evaluated
data
acquisition
modes
including
PASEF
data-dependent
(DDA
PASEF),
data-independent
(diaPASEF),
or
parallel
reaction
monitoring
(prm-PASEF)
as
well
processing
strategies.
By
employing
newly
ABPP
workflow,
successfully
identified
PSDEs
at
concentration
low
10
parts
per
billion
(ppb)
substance
sample.
Finally,
new
enabled
us
detect
PSDE
that
could
not
be
detected
original
PS
root-cause
investigation.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 21, 2024
ABSTRACT
Plants
rapidly
respond
to
environmental
changes
ensure
an
optimal
balance
between
growth
and
survival
with
intact
genome.
Here,
we
show
that
a
DNA
damage
response
gene,
which
named
LIFERING
,
is
under
the
direct
independent
regulation
of
ATM/ATR-SOG1
RBR
pathways.
We
demonstrate
upon
plays
essential
role
in
maintaining
cell
proliferation
death.
Downstream
RBR,
it
required
maintain
proliferation,
damaging
agents
initiates
death
accompanied
by
rapid
elongation
differentiation
transit
amplifying
cells
root
meristem.
RING-between-RING
E3
ligase;
its
ligase
activity
dependent
on
Cys392
residue
located
BRcat
domain,
responsible
for
coordination
zinc
ion
binding.
Using
proximity
labelling,
identified
acyl-CoA
dehydrogenase-like
protein
IBR3,
involved
conversion
indole-3-butyric
acid
(IBA)
indole-3-acetic
(IAA),
as
one
targets.
provide
evidence
IBR3
ubiquitinated
at
several
Lys
residues
presence
LIFERING.
Our
findings
responds
via
ubiquitination
likely
be
free-auxin
level,
indicating
link
auxin
root.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 26, 2024
Abstract
Polyglutamylation,
a
post-translational
modification
(PTM)
catalyzed
by
subset
of
Tubulin
Tyrosine
Ligase-Like
(TTLL)
family
enzymes,
regulates
microtubule
dynamics
through
its
influence
on
interactions
with
microtubule-associated,
motor,
and
severing
proteins,
has
recently
also
been
implicated
in
genetic
neurodegenerative
diseases.
In
this
study,
we
characterized
the
glutamylation
activity
various
glutamylating
TTLLs
human
embryonic
kidney
293T
(HEK293T)
cells,
revealing
distinct
patterns
mono-
polyglutamylation
among
TTLL
members,
TTLL4
TTLL11
exhibiting
strongest
chain
initiation
elongation
activities,
respectively.
We
found
that
TTLL6
expression
uniquely
decreased
stability,
live-cell
imaging
end-binding
protein
(EB3)
showing
TTLL6-induced
decrease
stability.
To
explore
therapeutic
modulation
activity,
tested
LDC10,
novel
inhibitor,
which
successfully
blocked
across
all
investigated
while
reversing
microtubule-destabilizing
effects
TTLL6.
These
findings
identify
potential
pathogenic
role
highlight
LDC10
as
promising
pharmacological
tool
to
counteract
TTLL-induced
destabilization.
The Plant Journal,
Год журнала:
2024,
Номер
120(5), С. 1735 - 1750
Опубликована: Ноя. 21, 2024
SUMMARY
Heat
is
a
critical
environmental
stress
for
plant
survival.
One
of
its
harmful
effects
on
the
cells
disruption
genome
integrity.
However,
mechanisms
by
which
plants
cope
with
heat‐induced
DNA
damage
remain
largely
unknown.
RMI1,
component
RTR
(RECQ4‐TOP3α‐RMI1)
complex,
plays
pivotal
role
in
maintaining
stability.
In
this
study,
we
identified
target
gene
RMI1
characterizing
high‐temperature‐sensitive
mutant.
The
growth
and
development
rmi1‐1
seedlings
carrying
non‐frameshift
mutation
were
hindered
at
38°C.
Abnormal
mitotic
chromosome
behaviours
ultimately
led
to
cell
death
root
tips.
Additionally,
presence
fragments
during
anaphase
I
caused
pollen
abortion
sterility
plants.
Yeast
two‐hybrid
assays
revealed
that
interactions
between
RMI1‐1
RECQ4
or
TOP3α
weakened
increasing
temperature
entirely
ceased
36°C.
contrast,
functional
maintained
under
same
conditions.
These
results
indicate
disrupts
formation
complex
high
temperatures,
leading
defects
repair
increased
sensitivity
heat
stress.
embryos
rmi1‐cr2
mutant
frameshift
exhibited
complete
lethality.
addition,
overexpression
enhanced
tolerance
rice.
findings
provide
insights
into
molecular
responds
temperatures
stability
