lec 6-7 cell cycle and cell polarity Flashcards
defects in cell division
lead to chromosome abnormalities
when is the genome replicated (eukaryotic)
S phase
what is the order of the cell cycle
G1
S
G2
M
G1
commitment to cell division
cell grows in size
synthesises mRNA and proteins (histones) required for DNA synthesis
checkpoint before S phase
- formation of G1/S cyclin with Cdk
- is environment suitable e.g. pH
- integrity of DNA assessed
if a cell does not clear to pass through to S phase..
enters G0, dormant phase
- no cell growth or division
G2
rapid cell growth and protein synthesis
preparation for mitosis
checkpoint:
G2/M
- checks for damage
if damage signals activate p53
Cdk1 inhibited
cell cycle does not progress
hartwell discovered
checkpoints using budding yeast
paul nurse discovered
cdk and regulators using fission yeast
hunt discovered
cyclins using sea urchins
Wee1
kinase
influences cell size
inhibits entry of cell cycle into mitosis
inhibits cdk1 by phosphorylation
proteolysis
degradation of a protein
mitosis
segregation of equal numbers of chromosomes into each daughter cell
2 genetically identical daughter cells
outline steps of mitosis
DNA condenses centrosome duplicates microtubules terminate and attach to chromosomes chromosomes align on mitotic spindle separate to opposite ends
3 types of microtbule making up mitotic spindle
astral
interpolar
kinetochore
astral microtubules
anchor the spindle poles to the cell membrane
interpolar microtubules
overlap/interlock and the spindle midzone
keep poles at correct distance apart
kinetochore microtubules
mediate attachment of kinetochore microtubules to chromosome via kinetochore complex (attachment site)
chromosome movement
microtubule polymerisation
kinetochore microtubules shorten and draw chromosomes towards spindle poles
role of microtubules in cytokinesis
position plane of division
contractile ring drives cleavage (actin and myosin motor protein also involved)
s phase
DNA replication
M phase
mitosis - nuclear division
cytokinesis - cytoplasmic division
checkpoint 3 - are all chromosomes properly attached to mitotic spindle?
activation of cdk
activated by cyclins
cyclin concentration oscillates during cell cycle
causes cell cycle to progress
cdc2
cell division cycle protein 2 - same as cdk1
negative regulator of cell division
Wee1 - kinase
Cdc25
phosphotase
positive regulator of cell division
stimulates cdc2/cdk1
progression of cell cycle
ndc80
protein ring complex
attaches to kinetochore and microtubule
leaves space in between for microtubule polymerisation
amphitelic attachment
- Each kinetochore is attached to microtubules from opposing spindle poles
- monomers of intermediate filaments interact in both parallel and anti-parallel manners to form dimers
syntelic attachment
- Both sister kinetochores are attached to MTs from the same spindle pole
monotelic
- One kinetochore is attached to a MT from a spindle pole and the other kinetochore is not attached to a MT
spindle assembly checkpoint - SAC
in M phase
checks all microtubules are properly attached to the spindle
polarity
having one end morphologically/funcionally different from the other
why is polarity necessary
cellular morphogenesis
tissue morphogenesis
organism morphogenesis
4 main examples of polarisation mechanisms
neuronal guidance
assymetrical cell division
yeast mating
cell migration
how is cell polarity acheived
cytoskeletal remodelling
signal pathways converge on actin and microtubule cytoskeletons
reassembly of filaments at new sites
taxis
motion of orientation of a cell/organism in response to an external stimulus
GEFs
proteins that activate GTPases by stimulating release of GDP
GDIs
bind to GDP-bound GTPases and prevent exchange
guidance cue
something that attracts or repels the cell
either contact/adhesion or chemical
recognised by receptors on growth cones (structure at tip)
contact/adhesion guidance cues
proteins form a substrate on which the cell can crawl
ECM
often short-range
e.g. cadherins attract
chemical guidance cues
secreted
often long-range
e.g. netrins attract, semaphorins repel
commissural neurons
use guidance cues to project onto the other side of the CNS
ensure left-right synchronisation
DDC receptors for netrin
once activated, lead to signal cascade
growth cones crawls in direction of ventral midline in brain
slit protein
has opposite effect to netrin, prevents neurons crossing midline again
secreted by floor plate
role of GPCR
to transduce an extracellular signal to a small GTPase to cause a cellular response
examples of small monomeric GTPases
Rho
Ras
substrate level phosphorylation
metabolic process
results in ATP/GTP formation by direct transfer of a phosphate group
central regulator or cell polarity
cdc42
par proteins
responsible for asymmetric positioning of mitotic spindle
help polarise tissues
relocalise over time
e.g. LBK1 is a human par protein
epithelial apical-based polarity
plasma membrane of epithelial cells is divided into two domains
splits top and bottom
what separates apex and baso-lateral surface
tight junctions
apical surface
permeable to water-soluble molecules
surface area can be increased
faces externally
basolateral surface
impermeable
faces internally
in contact with blood supply
2 complexes associated with par proteins
scribble and crumbs
role of par proteins
kinases - switch other proteins on/off
scaffolding factors interact and recruit other proteins
