Cell cycle Flashcards
stage where DNA synthesis occur
S phase
Stage where mitosis and cytokineses takes place
M phase
between M phase and S phase
G1 phase
between S phase and mitosis.
G2 phase
Sequential phases that creates Interphase
G1, S, G2
Cell growth occurs throughout the cell cycle, except during ___
Mitosis
provide time for the cell to monitor the internal and external environment to ensure that conditions are suitable and preparations are complete before the cell commits itself to the major upheavals of S phase and mitosis
Gap phases
Specialized resting state
G0
biochemical dissection of cell-cycle control mechanisms
Xenopus laevis (Italicized)
is useful for the genetic analysis of mechanisms underlying the control and coordination of cell growth and division in multicellular organisms
Drosophila melanogaster (italicize)
Several organisms used in the analysis of eukaryotic cell cycle
- The budding yeast Saccharomyces cerevisiae
- fission yeast Schizosaccharomyces pombe
thymidine analogs that incorporated DNA of dividing cells during the S-phase
BrdU (Bromodeoxyuridine)
allows the rapid and automatic analysis of large numbers of cells
Flow cytometer
operates much like a timer that triggers the events of the cell cycle in a set sequence
Cell-cycle control system
(on/off ) and launch events in a complete, irreversible fashion
Binary
Three regulatory transitions
- Start in late G1
- G2/M transition
- Metaphase-to-Anaphase transition
cell commits to cell-cycle entry and chromosome duplication
Start (restriction point) in late G1
triggers the early mitotic events that lead to chromosome alignment on the mitotic spindle in metaphase
G2/M transition
stimulates sister-chromatid separation; completion of mitosis and cytokinesis
Metaphase-to-anaphase
central components of cell-cycle control system
Cyclin-dependents kinases (Cdks)
are controlled by cyclins
Cdks
Four classes of cyclins
- G1/S-cyclin
- S-cyclins
- M-cyclins
- G1-cyclins
activate Cdks in late G1
G1/S-cyclin
bind Cdks soon after progression through Start and help stimulate chromosome duplication
S-cyclins
activate Cdks that stimulate entry to mitosis at the G2/M transition
M-cyclins
govern the activities of the G1/S-cyclins
G1-cyclins
How many Cdks in vertebrates
Four Cdks
four Cdks in Vertebrates
- two – G1-cyclins
- one – G1/S- and S-cyclins
- one – S- and M-cyclins
active site in the Cdk protein is partly obscured by a protein loop
Absence of cyclin
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
What happens when Cdk protein is partially obscured by a protein loop
Absense of cyclin
When the loop moved away from the active site, what will happen to Cdk?
Partial activation of Cdk enzyme
phosphorylates an amino acid near the entrance of the Cdk active site
Cdk-activating kinase (CAK)
a protein kinase that inhibits Cdk activity
Wee1 protein kinase
a phosphatases that dephosphorylates the site, increasing Cdk activity
Cdc25 phosphatases
inactivated cyclin-Cdk complexes
Cdk inhibitor proteins (CKIs)
The key regulator that Triggers the Metaphase-to-Anaphase Transition
- a member of the ubiquitin ligase family of enzymes.
Anaphase-promoting complex/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/S-cyclins in early S phase
SCF
- increases in mid-mitosis and remains high through G1
- changes in its association
with an activating subunit
APC/C activity
APC/C activity depends on what subunits?
- Cdc20 or Cdh1
substrate-binding subunits called F-box proteins; constant during cell cycle
SCF activity
in early animal embryos – cell-cycle depends exclusively on ____ _____ that involve the regulation of Cdks and ubiquitin ligases and their target proteins
Post-transcriptional mechanisms
A phase where DNA duplication occurs
- occur with extreme accuracy
- every nucleotide in the genome must be copied once
S phase
Where DNA replication in eukaryotic cell begins
Origins of Replication
unwinds the double
helix
DNA helicase
replication machinery moves outward from the origin at two replication forks
Elongation phase
two distince steps of Inititaion of DNA initiation
- Only in Late mitosis or Early G1
- S phase
two inactive DNA helicases
Mcm helicases
___ → licensing of
replication origins
preRC (prereplicative complex)
DNA helicase are activated →DNA unwinding and initiation of DNA synthesis
S phase
stimulate a large increase in the synthesis of the four histone subunits that form the histone octamers
S-Cdks
helps to control gene expression
Chromatin packaging
the chromatin that is highly condensed
Heterochromatin
a chromatin that has more open structure
Eurochromatin
where cohesin of sister-chromatid depends
Cohesin
two subunits of cohesin
SMC proteins
- 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.
- promotes breakdown of nuclear envelope
M-Cdk
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
Aurora kinases-A
controls attachment of sister chromatids to the spindle
Aurora kinases-B
How does M-Cdk activation begins?
Accumulation of M-cyclin
Activatation of ____ , removes inhibitory phosphatase that restrain M-Cdk
Cdc25
Activator of M-Cdk
Cdc5
Inhibitor of M-Cdk
Wee1
chromatids are compacted
Chromosome condensation
two sisters are resolved into distinct, separable units
Sister-chromatid resolution
Where condensation and resolution of sister-chromatic depends
- A five-subunit protein complex
Condensin
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 called kinetochores
Kinetochore microtubules
radiate outward from the poles and contact cell cortex
Astral microtubules
consists of a cloud of pericentriolar matrix that surrounds a pair of
centrioles
Centrosome
coiled-coil proteins that link the motors to the centrosome, structural proteins, and components of the cell-cycle control system
Microtubule-dependent motor proteins
move toward the plus ends
- slide the two antiparallelmicrotubules 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
Kinesi-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
M-Cdk phosphorylates several subunits of the nuclear pore complexes
Nuclear-envelope breakdown
catastrophe or rescue
Microtubule dynamic instability
promote stability and
catastrophe factors that destabilize microtubule plus ends
Microtubule-associated proteins (MAPs)
____ play an active part in spindle formation – by creating a local environment that favors both microtubule nucleation and microtubule stabilization
Chromosomes
bound to the chromatin → activated Ran-GTP – releases microtubule-stabilizing proteins → nucleation and stabilization of microtubules around chromosomes
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 chromosome
sister chromatids in a pair attach to opposite poles of the mitotic spindle
Bi-orientation
corrected by a system of trial and error
incorrect attachments
how does the kinetochore sense a correct attachment?
tension
securin binds to and inhibits the activity of a protease called _____
separase
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
- initial poleward movement of the chromosomes
Anaphase A
separation of the spindle poles themselves
Anaphase B
the two sets of chromosomes are packaged into a pair of daughter nuclei
Telophase
disassembly of ____ ____→ reformation of the nuclear envelope
mitotic spindle
promotes spindle assembly, chromosome condensation, and nuclear envelope breakdown
Phosphorylation by M-Cdk
division of the cytoplasm in two
Cytokinesis
Cytokinesis begins in an animal cell with the appearance of
Cleavage furrow
The structure underlying this process in cleavage furrow
Contractile ring
local formation of actin filaments depends on
Formin
parallel arrays of linear, unbranched actin filaments
Formin
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
How does the mitotic spindle specify the site of division?
1st : Astral stimulation model
2nd: Central spindle stimulation model
3rd: 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
- cortical relaxation is minimal at the spindle equator; promoting cortical contraction
Astral relaxation model
in central spindle stimulation model… the ____ ____, or _____ ____, generates a furrow-inducing signal that specifies the site of furrow formation at the cell cortex
spindle midzone
central spindle
higher-plant cells are enclosed by a semirigid
Cell wall
the cytoplasm of the plant cell is _____ from the inside out
partitioned
a new cell wall in plant
Cell wall
a structure that guide the assemply of cell plate during late anaphase
Phragmoplast
are usually present in large enough numbers; double once each cycle
Mitochondria and Chloroplasts
is cut into two during cytokinesis
ER
is reorganized and fragmented during mitosis
Golgi apparatus
A cell in which multiple nuclei share the same cytoplasm is called a
Syncytium
membranes are created around each nucleus in one round of coordinated cytokinesis
Cellularization
the genomes of two parents mix to generate offspring that are genetically distinct from either parent
Meiosis
- contain two slightly different copies, or homologs, of each chromosome, one from each parent
Diploids
carrying only a single copy of each chromosome → gametes
haploid
formed during the fusing of sperm and egg fuse
Zygote
Unique to meiosis, of segregating the homologs
Meiosis I
no further DNA replication; the sister chromatids pulled apart and segregated
Meiosis II
duplicated paternal and maternal homologs pair up alongside each other
Pair of homologs
prolonged period; homologs begin pairing
Meiotic prophase
interactions between pairing sites
Pairing
- 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
The paired homologs are brought into close juxtaposition, with their structural axes (___ ___)
Axial cores
Bridges the gap
- created by closely packed of transverse filaments
Synaptonemal complex
The five sequential stages of Meiotic prophase
Leptotene
Zygotene
Pachytene
Diplotene
Diakinesis
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
inter-homolog
connections
chiasmata
Three features of meiosis that distinguishes it from mitosis
- Both sister kinetochores in a homolot must attach stably to the same spindle pole
- Crossovers
- Cohesion is removed in anaphase I
cohesins near the centromeres are protected from separase in meiosis I by a kinetochore-associated protein called
Shugoshin
Functions of crossing-over
- helps hold homologs together
- Contributes to genetic diversification
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
