Viruses,
Journal Year:
2023,
Volume and Issue:
15(1), P. 241 - 241
Published: Jan. 14, 2023
ADP-ribosylation
(ADPRylation)
is
a
versatile
posttranslational
modification
in
eukaryotic
cells
which
involved
the
regulation
of
wide
range
key
biological
processes,
including
DNA
repair,
cell
signalling,
programmed
death,
growth
and
development
responses
to
biotic
abiotic
stresses.
Members
poly(ADP-ribosyl)
polymerase
(PARP)
family
play
central
role
process
ADPRylation.
Protein
targets
can
be
modified
by
adding
either
single
ADP-ribose
moiety
(mono(ADP-ribosyl)ation;
MARylation),
catalysed
mono(ADP-ribosyl)
transferases
(MARTs
or
PARP
"monoenzymes"),
may
decorated
with
chains
multiple
moieties
(PARylation),
via
activities
"polyenzymes".
Studies
have
revealed
crosstalk
between
PARylation
(and
lesser
extent,
MARylation)
processes
plants
plant-virus
interactions,
suggesting
that
these
tight
links
represent
novel
factor
regulating
plant
antiviral
immunity.
From
this
perspective,
we
go
through
literature
linking
PARylation-associated
other
pathways
controlling
virus
resistance.
Once
unraveled,
serve
as
basis
innovative
strategies
improve
crop
resistance
viruses
under
challenging
environmental
conditions
could
mitigate
yield
losses.
Cell,
Journal Year:
2023,
Volume and Issue:
186(21), P. 4475 - 4495
Published: Oct. 1, 2023
ADP-ribosylation
is
a
ubiquitous
modification
of
biomolecules,
including
proteins
and
nucleic
acids,
that
regulates
various
cellular
functions
in
all
kingdoms
life.
The
recent
emergence
new
technologies
to
study
has
reshaped
our
understanding
the
molecular
mechanisms
govern
establishment,
removal,
recognition
this
modification,
as
well
its
impact
on
organismal
function.
These
advances
have
also
revealed
intricate
involvement
human
physiology
pathology
enormous
potential
their
manipulation
holds
for
therapy.
In
review,
we
present
state-of-the-art
findings
covering
work
structural
biology,
biochemistry,
cell
clinical
aspects
ADP-ribosylation.
Molecular Cell,
Journal Year:
2023,
Volume and Issue:
83(13), P. 2303 - 2315.e6
Published: June 29, 2023
Modification
of
nucleic
acids
by
ADP-ribosylation
is
catalyzed
various
ADP-ribosyltransferases,
including
the
DarT
enzyme.
The
latter
part
bacterial
toxin-antitoxin
(TA)
system
DarTG,
which
was
shown
to
provide
control
DNA
replication
and
growth
as
well
protection
against
bacteriophages.
Two
subfamilies
have
been
identified,
DarTG1
DarTG2,
are
distinguished
their
associated
antitoxins.
While
DarTG2
catalyzes
reversible
thymidine
bases
employing
a
macrodomain
antitoxin,
activity
biochemical
function
its
NADAR
domain,
yet
unknown.
Using
structural
approaches,
we
show
that
DarT1-NADAR
TA
for
guanosine
bases.
DarT1
evolved
ability
link
ADP-ribose
guanine
amino
group,
specifically
hydrolyzed
NADAR.
We
de-ADP-ribosylation
also
conserved
among
eukaryotic
non-DarT-associated
members,
indicating
wide
distribution
modifications
beyond
DarTG
systems.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: June 2, 2023
Abstract
In
the
mammalian
DNA
damage
response,
ADP-ribosylation
signalling
is
of
crucial
importance
to
mark
sites
as
well
recruit
and
regulate
repairs
factors.
Specifically,
PARP1:HPF1
complex
recognises
damaged
catalyses
formation
serine-linked
marks
(mono-Ser-ADPr),
which
are
extended
into
ADP-ribose
polymers
(poly-Ser-ADPr)
by
PARP1
alone.
Poly-Ser-ADPr
reversed
PARG,
while
terminal
mono-Ser-ADPr
removed
ARH3.
Despite
its
significance
apparent
evolutionary
conservation,
little
known
about
in
non-mammalian
Animalia
.
The
presence
HPF1,
but
absence
ARH3,
some
insect
genomes,
including
Drosophila
species,
raises
questions
regarding
existence
reversal
serine-ADP-ribosylation
these
species.
Here
we
show
quantitative
proteomics
that
Ser-ADPr
major
form
response
melanogaster
dependent
on
d
Parp1:
Hpf1
complex.
Moreover,
our
structural
biochemical
investigations
uncover
mechanism
removal
Parg.
Collectively,
data
reveal
PARP:HPF1-mediated
a
defining
feature
DDR
striking
conservation
within
this
kingdom
suggests
organisms
carry
only
core
set
ADP-ribosyl
metabolising
enzymes,
such
,
valuable
model
study
physiological
role
signalling.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 24, 2024
Abstract
Host-pathogen
conflicts
are
crucibles
of
molecular
innovation.
Selection
for
immunity
to
pathogens
has
driven
the
evolution
sophisticated
mechanisms
throughout
biology,
including
in
bacteria
that
must
evade
their
viral
predators
known
as
bacteriophages.
Here,
we
characterize
a
widely
distributed
anti-phage
defense
system,
CmdTAC,
provides
robust
against
infection
by
T-even
family
phages.
Our
results
support
model
which
CmdC
detects
sensing
capsid
proteins,
ultimately
leading
activation
toxic
ADP-ribosyltransferase
effector
protein,
CmdT.
We
show
newly
synthesized
protein
triggers
dissociation
chaperone
from
CmdTAC
complex,
destabilization
and
degradation
antitoxin
CmdA,
with
consequent
liberation
CmdT
ADP-ribosyltransferase.
Strikingly,
does
not
target
DNA,
or
structured
RNA,
targets
other
ADP-ribosyltransferases.
Instead,
modifies
N6
position
adenine
GA
dinucleotides
within
single-stranded
RNAs
arrest
mRNA
translation
inhibition
replication.
work
reveals
new
mechanism
anti-viral
previously
unknown
but
broadly
class
ADP-ribosyltransferases
mRNA.
Biochemical Journal,
Journal Year:
2022,
Volume and Issue:
479(4), P. 463 - 477
Published: Feb. 17, 2022
ADP-ribosylation
has
primarily
been
known
as
post-translational
modification
of
proteins.
As
signalling
strategy
conserved
in
all
domains
life,
it
modulates
substrate
activity,
localisation,
stability
or
interactions,
thereby
regulating
a
variety
cellular
processes
and
microbial
pathogenicity.
Yet
over
the
last
years,
there
is
increasing
evidence
non-canonical
forms
that
are
catalysed
by
certain
members
ADP-ribosyltransferase
family
go
beyond
traditional
protein
signalling.
New
macromolecular
targets
such
nucleic
acids
new
ADP-ribose
derivatives
have
established,
notably
extending
repertoire
Based
on
physiological
relevance
so
far,
deserves
its
recognition
next
to
which
we
therefore
review
following.
Journal of Medicinal Chemistry,
Journal Year:
2022,
Volume and Issue:
65(11), P. 7532 - 7560
Published: May 24, 2022
Major
advances
have
recently
defined
functions
for
human
mono-ADP-ribosylating
PARP
enzymes
(mono-ARTs),
also
opening
up
potential
applications
targeting
them
to
treat
diseases.
Structural
biology
combined
with
medicinal
chemistry
has
allowed
the
design
of
potent
small
molecule
inhibitors
which
typically
bind
catalytic
domain.
Most
these
are
at
early
stages,
but
some
already
a
suitable
profile
be
used
as
chemical
tools.
One
compound
PARP7
even
progressed
clinical
trials.
In
this
review,
we
collect
mono-ARTs
typical
"H–Y−Φ"
motif
(Φ
=
hydrophobic
residue)
and
focus
on
compounds
that
been
reported
active
against
one
or
restricted
number
enzymes.
We
discuss
from
point
view
include
an
analysis
available
crystal
structures,
allowing
us
craft
pharmacophore
model
lays
foundation
obtaining
new
more
specific
inhibitors.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 13, 2024
Abstract
Bacteria
defend
against
phage
infection
via
a
variety
of
antiphage
defense
systems.
Many
systems
were
recently
shown
to
deplete
cellular
nicotinamide
adenine
dinucleotide
(NAD
+
)
in
response
infection,
by
breaking
NAD
ADP-ribose
(ADPR)
and
nicotinamide.
It
was
demonstrated
that
depletion
during
deprives
the
from
this
essential
molecule
impedes
replication.
Here
we
show
substantial
fraction
phages
possess
enzymatic
pathways
allowing
reconstitution
its
degradation
products
infected
cells.
We
describe
pathway
1
(NARP1),
two-step
which
one
enzyme
phosphorylates
ADPR
generate
ADPR-pyrophosphate
(ADPR-PP),
second
conjugates
ADPR-
PP
.
Phages
encoding
NARP1
can
overcome
diverse
set
systems,
including
Thoeris,
DSR1,
DSR2,
SIR2-HerA,
SEFIR,
all
as
part
their
defensive
mechanism.
Phylogenetic
analyses
is
primarily
encoded
on
genomes,
suggesting
phage-
specific
function
countering
bacterial
defenses.
A
pathway,
NARP2,
allows
defenses
building
metabolites
different
than
ADPR-PP.
Our
findings
report
unique
immune
evasion
strategy
where
viruses
rebuild
molecules
depleted
thus
overcoming
host
immunity.
Biomolecules,
Journal Year:
2022,
Volume and Issue:
12(3), P. 443 - 443
Published: March 13, 2022
Cellular
functions
are
regulated
through
the
gene
expression
program
by
transcription
of
new
messenger
RNAs
(mRNAs),
alternative
RNA
splicing,
and
protein
synthesis.
To
this
end,
post-translational
modifications
(PTMs)
proteins
add
another
layer
complexity,
creating
a
continuously
fine-tuned
regulatory
network.
ADP-ribosylation
(ADPr)
is
an
ancient
reversible
modification
cellular
macromolecules,
regulating
multitude
key
functional
processes
as
diverse
DNA
damage
repair
(DDR),
transcriptional
regulation,
intracellular
transport,
immune
stress
responses,
cell
survival.
Additionally,
due
to
emerging
role
in
pathological
processes,
ADP-ribosyltransferases
(ARTs),
enzymes
involved
ADPr,
attracting
growing
interest
drug
targets.
In
review,
overview
human
ARTs
their
related
biological
provided,
mainly
focusing
on
regulation
ADP-ribosyltransferase
Diphtheria
toxin-like
(ARTD)-dependent
functions.
Finally,
order
unravel
novel
relationships,
we
propose
analysis
inventory
clusters,
including
ARTDs,
which
share
conserved
sequences
at
3′
untranslated
regions
(UTRs).