CELL CYCLE Flashcards
cycle of duplication and division
cell cycle
main goal of cell division
the passing on of its genetic information to the next generation of cells
basic concept of cell cycle
duplicate DNA and then segregate into two copies
two main phases of cell cycle
S phase (DNA synthesis) and M phase(mitosis and cytokinesis)
provide time for the cell to monitor the internal and external environment to ensure that conditions are suitable and preparations are complete
gap phases
two stages of gap phase
G1 phase and G2 phase
specialized resting state when cell cycle needs to reset
G0 phase
commitment point near the end of G1
restriction point
stain that helps identify the S phase of the cell cycle
bromodeoxyuridine (BrdU)
cell stain that measures the DNA content
flow cytometer
cell cycle is _______ (irreversible)
binary
checks every phase of the cell cycle, ensuring there is no error
biochemical switches
three major regulatory transitions
- Start (restriction point)
- G2/M transition
- metaphase-to-anaphase
stimulates sister-chromatid separation; completion of mitosis and cytokinesis
metaphase-to-anaphase
triggers the early mitotic events that lead to chromosome alignment on the mitotic spindle in metaphase
G2/M transition
cell commits to cell-cycle entry and chromosome duplication
metaphase-to-anaphase
cyclical changes in the phosphorylation of intracellular proteins that initiate or regulate the major events of the cell cycle
cyclin-dependent kinases (Cdks)
controls cyclin-dependent kinases
cyclins
four classes of cyclins
- G1/S-cyclin
- S-cyclins
- M-cyclins
- G1-cyclins
bind Cdks soon after progression through Start and help stimulate chromosome duplication
S-cyclins
govern the activities of the G1/S-cyclins
G1-cyclins
activate Cdks in late G1
G1/S-cyclin
activate Cdks that stimulate entry to mitosis at the G2/M transition
M-cyclins
causes the loop to move away from the active site, resulting in partial activation of the Cdk enzyme
cyclin binding
a separate kinase, the Cdk-activating kinase (CAK), phosphorylates an amino acid near the entrance of the Cdk active site
full activation
active site in the Cdk protein is partly obscured by a protein loop
absence of cyclin
phosphorylates → inhibits
Wee1 protein kinase
dephosphorylates → activate/increase
Cdc25 phosphatase
inactivated cyclin-Cdk complexes
Cdk inhibitor proteins (CKIs)
progression through the metaphase- toanaphase transition is triggered by:
protein destruction
ubiquitin ligase to stimulate the proteolytic destruction of specific regulatory proteins by proteosomes; polyubiquitylate
anaphase-promoting complex or cyclosome (APC/C)
protect the protein linkages that hold sister-chromatid pairs together in early mitosis; destroyed at metaphase
securin
destruction inactivates most Cdks in the cell; proteins are
dephosphorylated
S- and M-cyclins
ubiquitin ligase; ubiquitylate CKI proteins in late G1; destruction of G1/Scyclins in early S phase
SCF
changes in its association with an activating subunit—either Cdc20 in mid-mitosis or Cdh1 from late mitosis through early G1
APC/C activity
substrate-binding subunits called F-box proteins; constant during cell cycle
SCF activity
in early animal embryos – cell-cycle depends exclusively on ___________; involve the regulation of Cdks and ubiquitin ligases and their target proteins
post-transcriptional mechanisms
more complex cell cycles
transcriptional control
DNA replication phase
S phase
replication machinery moves outward from the origin at two replication forks
elongation phase
unwinds the DNA double helix
DNA helicase
highly condensed packaged chromatin
heterochromatin
more open packaged chromatin
euchromatin
sister-chromatid cohesion depends on:
cohesin
subunit of cohesion that forms giant ring-like structures
SMC proteins
stimulate a large increase in the synthesis of the four histone subunits that form the histone octamers
S-Cdks
stages of mitosis (cell duplication)
prophase, prometaphase, metaphase, anaphase, telophase, cytokinesis
induce the assembly of the mitotic spindle and ensure that each sister chromatid in a pair is attached to the opposite pole of the spindle.
M-Cdk
promotes the breakdown of the nuclear envelope and rearrangements of the actin cytoskeleton and the Golgi apparatus; triggered by M-Cdks
chromosome condensation
required for the normal assembly of a bipolar mitotic spindle
Polo-like kinase (Plk)
Helps control proteins that govern the assembly and stability of the spindle and controls attachment of sister chromatids to the spindle
Aurora kinases
M-Cdk activation begins with the accumulation of:
M-cyclin
M-Cdk’s ability to inhibit its own activator suggests that M-Cdk activation in mitosis involves:
positive feedback loops
two sisters are resolved into distinct, separable units
sister-chromatid resolution
sister-chromatid resolution depends on a five-subunit protein complex called
condensin
process in which depends on mitotic spindle
chromosome segregation
overlapped with the plus ends of microtubules from the other pole
interpolar microtubules
attached to sister-chromatid pairs at large protein structures
kinetochore microtubules
large protein structures where kinetochore microtubules attach to
kinetochores
radiate outward from the poles and contact cell cortex
astral microtubules
consists of a cloud of pericentriolar matrix that surrounds a pair of centrioles; contains γ-tubulin ring complexes
centrosome
move toward the plus ends; slide the two antiparallel microtubules past each other toward the spindle poles, pushing the poles apart
kinesin-5
are minus-end directed motors; cross-link antiparallel interpolar microtubules at the spindle midzone and tend to pull the poles together
kinesin-14
chromokinesins; plus-end directed motors that associate with chromosome arms and push the attached chromosome away from the pole
kinesin-4/10
minus-end directed motors; motors pull the spindle poles toward the cell cortex and away from each other
dynein
helps initiate centrosome duplication
G1/S-Cdk
spindle assembly begins in early mitosis and are pulled by _________; links astral microtubules to the cell cortex
dynein motor proteins
M-Cdk phosphorylates several subunits of the nuclear pore complexes
Nuclear-envelope breakdown
promote stability and catastrophe factors that destabilize microtubule plus ends
microtubule-associated proteins (MAPs)
bound to the chromatin; nucleation and stabilization of microtubules around chromosomes
guanine nucleotide exchange factor (GEF)
a giant, multilayered protein structure that is built at the centromeric region of the chromatid
kinetochore
rod-shaped protein complex; linking the microtubule to the kinetochore
Ndc80
microtubules in the vicinity of the chromosomes become embedded in the plus-end-binding sites of the kinetochore. Polymerization at these plus ends then results in growth of the microtubules away from the kinetochore.
absence of centrosome
sister chromatids in a pair attach to opposite poles of the mitotic spindle
bi-orientation
tension-sensing mechanism depends on the protein kinase:
Aurora-B
initiates sister-chromatid separation by ubiquitylating several mitotic regulatory proteins and thereby triggering their destruction
anaphase-promoting complex (APC/C)
phase where cohesins hold sister chromatids together
metaphase
phase where loss of sister-chromatid cohesion occurs
anaphase
blocks progression through the metaphase-to anaphase transition
spindle assembly checkpoint
unattached kinetochore acts like an enzyme that catalyzes a change in the conformation of Mad2 → can bind and inhibit Cdc20–APC/C
Mad2
sudden loss of sister-chromatid cohesion at the onset of anaphase
chromosome segregation
sub-phase of anaphase where initial poleward movement of the chromosomes
anaphase A
sub-phase of anaphase where separation of the spindle poles themselves
anaphase B
phase where the two sets of chromosomes are packaged into a pair of daughter nuclei
telophase
spindle disassembly and the re-formation of daughter nuclei
dephosphorylation
dephosphorylation and the completion of mitosis could be triggered by the
inactivation of Cdks, the activation of phosphatases, or both
final stage: division of the cytoplasm in two
CYTOKINESIS
local formation of actin filaments depends on
formin
protein components that assembles the contractile ring
actin and myosin II
persists as a tether between the two daughter cells and contains the remains of the central spindle
midbody
small GTPase of the Ras superfamily; controls the assembly and function of the contractile ring at the site of cleavage
RhoA
models that suggests the mitotic specificity of the site of division
- astral stimulation model
- central spindle stimulation model
- astral relaxation model
astral microtubules carry furrow inducing signals
astral stimulation model
the spindle midzone, or central spindle, generates a furrow-inducing signal that
specifies the site of furrow formation at the cell cortex
central spindle stimulation model
the astral microtubules promote the local relaxation of actin myosin bundles at the cell cortex
astral relaxation model
higher-plant cells are enclosed by a
semirigid cell wall
formation of the cell wall during plant cytokinesis is guided by the
phragmoplast
organelle that is reorganized and fragmented during mitosis
Golgi apparatus
organelle that is cut into two during cytokinesis
ER (endoplasmic reticulum)
the mother cell must first segregate ____________ to one side of the cell and then position the plane of division so that the appropriate daughter cell inherits these components
cell fate determinants
membranes are created around each nucleus in one round of coordinated cytokinesis
cellularization
cell which is carrying only a single copy of each chromosome → gametes
haploid
fusion of sperm and egg cell
zygote
contain two slightly different copies, or homologs of each chromosome, one from
each parent
diploid
the genomes of two parents mix to generate offspring that are genetically distinct from
either parent; reduces the chromosome number by half
MEIOSIS
duplicated paternal and maternal homologs pair up alongside each other
pair of homologs
stage with no further DNA replication; the sister chromatids pulled apart and segregated
meiosis II
four chromatid structure
bivalent
homolog pairs are then locked together by:
homologous recombination
the DNA of a chromatid crosses over to become continuous with the DNA of a homologous chromatid
crossovers
assembles on a double strand break in a chromatid, binds the matching DNA sequence in
the nearby homolog and helps reel in this partner
recombination complex
homologs condense and pair and genetic recombination begins
leptotene
synaptonemal complex begins to assemble at sites where the homologs are closely associated and recombination events are occurring
zygotene
assembly process is complete, and the homologs are synapsed along their entire lengths
pachytene
disassembly of the synaptonemal complexes and the concomitant condensation and shortening of the chromosomes
diplotene
segregation of homologs
diakinesis
meiotic prophase – five sequential stages
leptotene, zygotene, pachytene, diplotene, diakinesis
the individual crossover events between non-sister chromatids can be seen as inter-homolog connections
chiasmata (chiasma)
cohesins near the centromeres are protected from separase in meiosis I by a kinetochore-associated protein called
shugoshin
where DNA is accessible
hot spots
heterochromatin regions (centromeres and telomeres)
cold spots
the presence of one crossover event inhibits another from forming close by
crossover interference
when homologs fail to separate; some of the resulting haploid gametes lack a particular chromosome, while others have more than one copy of it
nondisjunction
trisomy 21
Down syndrome
stimulate cell growth; synthesis of proteins and other macromolecules
Growth factors
promote cell survival; suppressing apoptosis
Survival factors
organisms where the rate of proliferation depends on theavailability of nutrients
unicellular organisms
organisms where cells divide only when the organism needs more cells
multicellular organism
first mitogen identified; observation that fibroblasts in a culture dish proliferate when provided with serum not when provided with plasma
platelet-derived growth factor (PDGF)
acts not only on epidermal cells but also on many other cell types, including both epithelial and nonepithelial cells
epidermal growth factor (EGF)
only induces the proliferation of red blood cell precursors
erythropoietin
inhibitory extracellular signal proteins; inhibit proliferation
transforming growth factor-β (TGFβ)
cell cycle phase when neurons and skeletal muscles; cell-cycle control system is completely dismantled
terminally differentiated or G0 state
bind to specific DNA sequences in the promoters of a wide variety of genes that encode proteins required for S-phase entry
E2F proteins
in the absence of mitogenic stimulation, E2Fdependent gene expression is inhibited by an interaction between E2F and members of the:
retinoblastoma protein (Rb) family
a result of spontaneous chemical reactions in DNA, errors in DNA replication, or exposure to radiation or certain chemicals
DNA damage
acts as ubiquitin ligase that targets p53 for destruction
Mdm2
at undamaged cells, it is highly unstable and is present at very low concentration
p53
defect in ATM; very sensitive to x-rays and suffer from increased rates of cancer
ataxia telangiectasia
changes in the structures of the telomeres; synthesized by the enzyme telomerase; promotes the formation of protein cap structures that protect the chromosome ends
replicative cell senescence
programmed cell death; “falling off”
apoptosis
cells that die in response to an acute insult
cell necrosis
a form of programmed cell death that is triggered by a specific regulatory signal from other cells
necroptosis
have a cysteine at their active site and cleave their target proteins at specific aspartic acids
caspases
begin the apoptotic process; apoptotic signal → assembly of large protein complexes → dimers → protease activation
initiator caspases
inactive dimers; cleaved by an initiator caspase at a site in the protease domain → rearranged to active form → amplifying proteolytic cascade → kill the cell
executioner caspases
a protein that normally holds a DNA degrading endonuclease (iCAD) in an inactive form; its cleavage frees the endonuclease (CAD) to cut up the DNA in the cell nucleus
lamins
transmembrane proteins; extracellular ligand-binding domain, a single transmembrane domain, and an intracellular death domain
death receptors
help prevent the inappropriate activation of the extrinsic pathway of apoptosis
FLIP
depends on the release into the cytosol of mitochondrial proteins
intrinsic or mitochondrial pathway
released into the cytosol → binds to an adaptor protein called Apaf1 (apoptotic protease activating factor-1) → oligomerize into a wheel-like heptamer called an apoptosome → recruit initiator caspase-9 proteins
cytochrome c
major class of intracellular regulators of the intrinsic pathway
Bcl2 family
types of Bcl2 family involved in apoptosis
pro-apoptotic and antiapoptotic
includes Bcl2 and BclXL
antiapoptotic
involves effector Bcl2 family proteins and Bh3-only protein
pro-apoptotic
first identified in insect viruses (baculoviruses); encode IAP proteins to prevent a host cell that is infected by the virus from killing itself by apoptosis
inhibitors of apoptosis (IAPs)
destruction for proteosomes
polyubiquitylate caspases
chromosome translocation causes excessive production of the Bcl2 protein; B cell lymphoma
Bcl2 gene
genes that are inactivated when the conditions were few cells dies from apoptosis;
Fas death receptor or the Fas ligand
