Different cells divide at…..
different rates
What does the rate cells divide at depend on (5 points):
Embryonic vs adult (embryonic=faster) complexity of system necessity for renewal tumour cells divide more cant divide when differentiating
5 common abnormalities in cancer cells:
Aneuploidy-abnormal chromosome number/content
Mutations in oncogenes + tumour suppressor genes
chromosome instability
change in level of cell cycle regulators
inhibition of growth is lost
What is the cell cycle?
orderly sequence of steps when cell duplicates and then divides
What must the cell cycle be?
co-ordinated
can’t divide before duplication
What are the 2 stages of the cell cycle?
Mitosis
Interphase
4 reasons why mitosis is the most vulnerable part of the cell cycle?
Reduced metabolism
More susceptible to damage e.g. heat/chemical
Cant repair damage
Gene transcripton is silenced
If the whole cell cycle lasts 24 hours how long would mitosis be?
1 hour
-mitosis is short
4 phases of interphase and what happens in each one:
G0-cell cycle machinery dismantled + function carried out
G1-checkpoint (for organelles)
S-DNA/protein synthesis
G2-checkpoint (For DNA_
What does replication of organelles need to co-ordinate with?
mitochondrial DNA replication
What are centrosomes:
organelles comprised of 2 centrioles (9 triple microtubules) at 90 degrees
2 functions of centrosomes:
MTOC-microtubule organising centre
Attach to mitotic spindle
6 phases of mitosis:
PMAT Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis
What are the 2 main things that happen in prophase?
Chromatin condenses
centrosomes at apex of cell
Why is it useful for chromatin to condense?
Less likely for DNA damage//breaks
In prophase what do the condensed chromosomes consist of and why?
2 sister chromatids as chromosomes were duplicated in S phase
What is in the centre of these chromosomes?
centromeres + kinetochores
What does the mitotic spindle join?
the 2 centrosomes
What happens in early + late prometaphase?
Early: nuclear envelope breaksdown + chromosomes attach to spindle via kinetochores
Late: chromosomes line up in middle of cell
Which protein senses kinetochore tension?
CENP-E
By metaphase what has happened?
chromosomes are lined up at equator of cell (metaphase plate) attached to mitotic spindle
What happens in anaphase overall?
chromosomes are pulled apart
so 1 sister chromatid goes to each pole
once the chromatids arrive at poles they are called daughter chromosomes
What are the 2 stages in anaphase?
A + B
What happens in anaphase A vs B?
A
- breakdown of cohesin
- microtubules shorten
- chromatids to poles
B=2 movements
- chromatids to poles
- centrosomes move away from eachother
What is the function of the 2 movements in anaphase B?
try to get daughter chromosomes as far apart from eachother as possible
2 things that happen in telophase:
nuclear envelope reforms
contractile ring assembly
What is the contractile ring for and how does it do this?
splits cytoplasm
gets tigher + tighter until membrane fuses to form 2 cells
What is the contractile ring made of?
actin + myosin
What does the contractile ring form?
cleavage furrow
What happens in cytokinesis?
cells divide
What is the tail between the 2 daughter cells called?
midbody
2 options if something goes wrong during cell cycle at rest:
cell cycle arrest
apoptosis
When is the spindle assembly checkpoint?
between pro-metaphase and metaphase
How is the spindle assembly checkpoint stimulated?
senses completion of chromosomes lining up + spindle assembly
2 things required for the spindle assembly checkpoint:
CENP-E
BUBs
What do BUBs do?
dissociate from kinetochore when chromosomes properly attached to spindle
What could mis-attachment of microtubules to kinetochores cause?
aneuploidy
What is a normal attachment between a spindle and kinetochore called?
amphelic attachment
-no checkpoint signal generated
What could more than 2 centrosomes cause?
aneuploidy
What do anti-cancer therapies try to cause?
chromosome mig-segregations in cancer cells –> death
2 examples of anti-cancer therapies:
Checkpoint kinase inhibitors
Taxanes/vinca alkaloids
What do checkpoint inhibitors try to do?
dont allow checkpoints to detect errors so cancer cells progress with errors
What do taxanes/vinca alkaloids cause and why is this effective?
long term mitotic arrest=cells are most likely to be damaged during mitosis
Don’t these anti-cancer therapies affect normal body cells?
yes but cancer cells are rapidly dividing so should be proportionally affected more
How do tumours progress through G1, G2 and spindle assembly checkpoints?
G1=increase growth factor/growth factor receptors
G2=even with damaged DNA
Spindle assembly=not even attached properly–>aneuploidy
What do normal cells vs tumour cells do when they reach G0?
Normal cells=dismantle cell cycle machinery + carry out function
Cancer cells=keep going in cell cycle
Why do tumour cells keep going in the cell cycle?
increased growth factor stimuli???
What does exit from G0 require?
growth factors
What do growth factors cause?
intracellular signalling
How are growth factor receptors normally found?
monomeric inactive form
What happens when ligand binds to growth factor receptor?
receptors dimerise
kinase domains phosphorylate eachother
2 ways phosphorylation can alter protein function?
change confirmation thus activity
create docking site for proteins
What 2 things does receptor activation trigger?
kinase cascade + binding of adapter proteins
2 examples of cells that never divide:
Neurones
Cardiac myocytes
