FEBS Letters,
Год журнала:
2019,
Номер
593(20), С. 2853 - 2867
Опубликована: Сен. 26, 2019
Successful
genome
duplication
is
required
for
cell
proliferation
and
demands
extraordinary
precision
accuracy.
The
mechanisms
by
which
cells
enter,
progress
through,
exit
S
phase
are
intense
areas
of
focus
in
the
cycle
stability
fields.
Key
molecular
events
G1
division
cycle,
especially
origin
licensing,
essential
pre‐establishing
conditions
efficient
DNA
replication
during
subsequent
phase.
If
poorly
regulated
or
disordered,
then
can
be
compromised
leading
to
instability,
a
hallmark
tumorigenesis.
Upon
entry
into
phase,
coordinated
firing
progression
ensure
complete,
timely,
precise
chromosome
replication.
Both
progressions
controlled
master
protein
kinases
ubiquitin
ligases
that
govern
activity
abundance
factors.
In
this
short
review,
we
describe
current
understanding
recent
developments
related
entrance
with
particular
on
licensing
regulation
vertebrates.
Cell Death and Differentiation,
Год журнала:
2017,
Номер
25(1), С. 114 - 132
Опубликована: Ноя. 10, 2017
Activation
of
the
p53
tumor
suppressor
can
lead
to
cell
cycle
arrest.
The
key
mechanism
p53-mediated
arrest
is
transcriptional
downregulation
many
genes.
In
recent
years
it
has
become
evident
that
p53-dependent
repression
controlled
by
p53–p21–DREAM–E2F/CHR
pathway
(p53–DREAM
pathway).
DREAM
a
repressor
binds
E2F
or
CHR
promoter
sites.
Gene
regulation
and
deregulation
shares
mechanistic
characteristics
with
retinoblastoma
pRB
acts
through
elements.
However,
because
its
binding
elements,
regulates
larger
set
target
genes
leading
regulatory
functions
distinct
from
pRB/E2F.
p53–DREAM
controls
more
than
250
mostly
cycle-associated
functional
spectrum
these
targets
spans
G1
phase
end
mitosis.
Consequently,
downregulating
expression
gene
products
which
are
essential
for
progression
cycle,
participates
in
control
all
checkpoints
DNA
synthesis
cytokinesis
including
G1/S,
G2/M
spindle
assembly
checkpoints.
Therefore,
defects
contribute
general
loss
checkpoint
control.
Furthermore,
promotes
chromosomal
instability
aneuploidy
cancer
cells.
Also,
abrogated
human
papilloma
virus
HPV
E7
protein
linking
carcinogenesis
HPV.
Another
feature
downregulates
involved
repair
telomere
maintenance
as
well
Fanconi
anemia.
Importantly,
when
function
lost,
CDK
inhibitor
drugs
employed
treatment
such
Palbociclib,
Abemaciclib
Ribociclib
compensate
early
steps
upstream
cyclin/CDK
complexes.
summary,
plethora
genes,
therapy.
Annual Review of Biochemistry,
Год журнала:
2022,
Номер
91(1), С. 107 - 131
Опубликована: Март 23, 2022
DNA
replication
in
eukaryotic
cells
initiates
from
large
numbers
of
sites
called
origins.
Initiation
these
origins
must
be
tightly
controlled
to
ensure
the
entire
genome
is
precisely
duplicated
each
cell
cycle.
This
accomplished
through
regulation
first
two
steps
replication:
loading
and
activation
replicative
helicase.
Here
we
describe
what
known
about
mechanism
reactions
a
genetic,
biochemical,
structural
perspective,
focusing
on
recent
progress
using
proteins
budding
yeast.
Cancer Discovery,
Год журнала:
2023,
Номер
13(4), С. 910 - 927
Опубликована: Янв. 30, 2023
Abstract
The
human
papillomavirus
(HPV)
genome
is
integrated
into
host
DNA
in
most
HPV-positive
cancers,
but
the
consequences
for
chromosomal
integrity
are
unknown.
Continuous
long-read
sequencing
of
oropharyngeal
cancers
and
cancer
cell
lines
identified
a
previously
undescribed
form
structural
variation,
“heterocateny,”
characterized
by
diverse,
interrelated,
repetitive
patterns
concatemerized
virus
segments
within
cancer.
Unique
breakpoints
shared
across
variants
facilitated
stepwise
reconstruction
their
evolution
from
common
molecular
ancestor.
This
analysis
revealed
that
virus–host
concatemers
unstable
and,
upon
insertion
excision
chromosomes,
facilitate
capture,
amplification,
recombination
rearrangements.
Evidence
heterocateny
was
detected
extrachromosomal
intrachromosomal
DNA.
These
findings
indicate
driven
dynamic,
aberrant
replication
an
oncogenic
virus,
thereby
extending
known
HPV
integration
to
include
promotion
intratumoral
heterogeneity
clonal
evolution.
Significance:
Long-read
unreported
genomic
variation
heterogeneous,
rearrangements
tumor.
Heterocateny
genomes,
which
rearrangement,
amplification
DNA,
promotes
See
related
video:
https://vimeo.com/845407469
commentary
McBride
White,
p.
814.
article
highlighted
In
Issue
feature,
799
A
crucial
factor
in
maintaining
genome
stability
is
establishing
deoxynucleoside
triphosphate
(dNTP)
levels
within
a
range
that
optimal
for
chromosomal
replication.
Since
DNA
replication
relevant
to
wide
of
other
activities,
these
may
all
be
directly
or
indirectly
affected
when
dNTP
concentrations
deviate
from
physiologically
normal
range.
The
importance
understanding
consequences
genetic
disorders
disturb
levels,
and
strategies
inhibit
synthesis
cancer
chemotherapy
treatment
disorders.
We
review
here
how
abnormal
affect
discuss
the
stability.
Successful
cell
proliferation
requires
efficient
and
precise
genome
duplication
followed
by
accurate
chromosome
segregation.
The
Cdc10-dependent
transcript
1
protein
(Cdt1)
is
required
for
the
first
step
in
DNA
replication,
human
cells
Cdt1
also
during
mitosis.
Tight
cycle
controls
over
abundance
activity
are
critical
to
normal
development
stability.
We
review
here
recent
advances
elucidating
molecular
functions
both
origin
licensing
kinetochore–microtubule
attachment,
we
describe
current
understanding
of
regulation.
