Cell division Flashcards
What is contact inhibition of growth and how is it relevant to cancer?
Cells normally stop growing by sensing neighbouring cells
Tumours usually lack contact inhibition so don’t stop growing
What do cells have to do before they can divide?
Duplicate their genetic material
What is the most vulnerable part of the cell cycle?
Mitosis- happens quickly to avoid risk
What phase is a normal resting cell in?
G0
Where do cells enter the cell cycle?
Gap phase 1 (G1)
What follows G1 and what happens in that phase?
Synthesis (S) phase where duplication takes place
What happens once duplication has taken place?
It enters G2 (decision point) where the cell checks that everything is ok and ready to go into mitosis
What occurs in the S phase?
DNA replication
Protein synthesis: initiation of translation and elongation increased; capacity is also increased
Replication of organelles (centrosomes, mitochondria, Golgi etc)
What is a centrosome?
An organelle near the nucleus of a cell which contains the 2 centrioles and from which the spindle fibres develop in cell division
What are the two centrioles referred to as and what do they do?
The mother and daughter centrioles- they regulate the microtubule network to orchestrate cell division
What are centrioles made of?
Microtubules
What happens to the centrioles in the G1 phase?
Separation of mother and daughter centrioles
What happens once the centrioles separate?
They start to duplicate in the S phase- the mother centriole will produce a daughter and the daughter will produce a mother
What is there surrounding the centrioles?
Cloud of protein complexes- there are points where they make nucleating sites for the microtubules
What is nucleation?
When you put microtubules together
What happens at nucleating sites as the cell encounters a need for mitosis?
Microtubules start to grow from these points and form an array of microtubules
What are the 6 phases of mitosis?
Interphase Prophase Metaphase Anaphase Telophase Cytokinesis
What happens during prophase?
Condensation of duplicated DNA
Why does the duplicated DNA need to be condensed?
Minimise DNA damage during mitosis
How is the DNA condensed in prophase?
Double helices are wrapped around histones to form beads on a string form of a chromatin which compacts the chromatin from being 2nm wide to 11nm wide
The string is then further wrapped around itself to form 30nm fibres, these fibres are then extended as a scaffold forming a chromosome scaffold- compacting it to 300nm wide, it is then further wrapped until you end up with a chromosome
What is a centromere?
Constriction around the chromosomes (like a belt)
What is the kinetochore?
Complex of proteins found at the centromere and is a key regulator of processes around chromosomes in the cell cycle
What happens during late prophase?
Nuclear envelope breaks down which allows chromosomes to come out into the cytoplasm and centrosomes migrate to opposite sides and begin to organise the spindle
What is the role of the spindle?
Highway that guides the chromosomes to where they have to go
How does the spindle form?
Radial microtubule arrays (asters) form around each centrosome
Radial arrays meet
Polar microtubules form which form highways telling chromosomes where to go
What happens to chromosomes in metaphase?
The chromosomes that have leaked into the cytoplasm migrate to the centre of the cell with their pairs
How do chromosomes attach to the spindles during pro metaphase?
By their kinetochores- one microtubule array will attach to the kinetochore on one side and another will attach on the other side
How does the kinetochore know it is attached to the microtubules or not?
There are specialised proteins e.g. CENP-E which sense attachment
What are the three types of half spindle?
Kinetochore microtubule- bound to kinetochore
Polar microtubule- a microtubule that has met and connected with a microtubule from the other centrosome
Astral microtubule- a microtubule that is originating from the centrosome that doesn’t connect to a kinetochore
What happens in anaphase?
Paired chromatids separate to form two daughter chromatids
What is cohesin?
Protein complex that holds the sister chromatids tightly bound together
What happens in anaphase A?
Cohesin is broken down and microtubules get shorter and chromatids start moving towards the centrosomes
The daughter chromatids are pulled towards opposite spindle poles
What happens in anaphase B?
Daughter chromosomes migrate towards poles and spindle poles migrate apart
What happens in telophase?
Daughter chromosomes arrive at the pole and the nuclear envelope reassembles at each pole
Centrosomes are moved apart and cells try to revert to normal size
Condensation of material where cells are going to split and you get the assembly of contractile ring of actin and myosin filaments
The contractile ring then squeezes the cell so that it divides into two daughter cells
What is the cleavage furrow?
Where the cells are going to be cleaved
What is the last phase of mitosis?
Cytokinesis- insertion of new membrane at cleavage furrow
What is the midbody
Where the actin-myosin ring is formed
What does the cell have to check that everything is in place in terms of the cell cycle?
Checkpoints which prevent the cell from moving onto the next step of the cycle if everything isn’t correct
What is the checkpoint when the cell wants to exit metaphase and enter anaphase?
Spindle assembly checkpoint- senses the completion of chromosome alignment and also checks for spindle assembly
How does the spindle assembly checkpoint signal the completion of chromosome alignment?
The kinetochores have proteins that emit a signal when the kinetochore is not attached to microtubules and when the kinetochore attaches to the microtubules it stops emitting a signal
What are the main two proteins involved in the kinetochore signalling process?
CENP-E
BUB protein kinase
What do BUBs do?
Dissociate from kinetochore when chromatids are properly attached to the spindle, they then go on to signal progression to anaphase
What happens if there is a spindle assembly checkpoint defect?
Anaphase initiates before the spindle attaches properly and it results in abnormal division of the chromosomes between the daughter cells
What is the normal attachment of the two sister chromatids like?
A microtubule array on a centrosome is attached to the kinetochore of one sister chromatid and the microtubule array from another centrosome is attached to the kinetochore of the other chromatid- this allows the sister chromatids to be split apart and go to opposite poles
What is syntelic attachment?
Both the kinetochores are hooked by two microtubule arrays from the same centrosome
What is merotelic attachment?
There is more than one microtubule array attached to the same kinetochore- this means that one of the chromatids is being pulled in two different directions
What is monotonic attachment?
Only one of the kinetochores of one chromatid is attached to a microtubule array, the other kinetochore is unattached
What does misattachment lead to?
Aneuploidy
What happens if the centrosomes are not duplicated properly?
You could end up with 4 centrosomes in one cell- this can lead to abnormal attachment of the microtubule arrays to the kinetochores leading to abnormal cytokinesis
What is checkpoint exploitation clinically used for?
Cancer therapy- proliferation of tumour cells in inhibited by inducing gross chromosome mis-segregations
Give an example of checkpoint exploitation?
Kinetochore signalling tells the cell when metaphase is complete so if you have an inhibitor for this checkpoint then you can make the nucleus think that it’s correctly hooked onto microtubules which allow the cells to proceed into anaphase and can cause long term mitotic arrest which makes them vulnerable as it’ll lead to apoptosis
Where are the 3 cell cycle checkpoints?
During G1
Before mitosis- to check for DNA damage
Metaphase-anaphase checkpoint
How do tumours affect the cell cycle?
Normally when cells come out of G1 they enter G0
Tumours block the ability of cells to leave the cell cycle and enter G0- cell cycle keeps repeating
What triggers a cell to enter the cell cycle and divide?
Growth factors and intracellular signalling cascades
