Cell Cycle and its Regulation Flashcards
Which human cells divide the most?
Embryonic
What process do cells normally use to grow? (to grow in one direction and not the other, tumours lack this)
Contact inhibition of growth
What is the most vulnerable point of the cell cycle? Why
Mitosis, cells are more easily killed during this phase.
What happens to gene transcription during mitosis
It is completely silenced
What happens to metabolism during mitosis
Slows down
If you damage DNA during mitosis what can you do
Nothing, it can’t be repaired
When is DNA damage irreparable
During mitosis
What are the 2 major phases of the cell cycle
M phase and interphase
What is interphase divided into
G0 G1 S G2
What is G0
Cell cycle machinery disabled, the cell is just resting
What does the cell do during G1
The cell considers if its necessary to divide
Which is the quickest part of the cell cycle and why
Mitosis because the cell is so vulnerable
What is the main thing that happens during S phase
Synthesis of protein, DNA replication, organelle replication
What does the cell do during G2
The cell checks everything is okay and that everything has been doubled and is ready to go into mitosis
What does centrosome consist of
2 centrioles
What is a centriole made of
Barrels of 9 triplet microtubules
What are the two main functions of a centriole
The microtubule organising centre (MTOC) and the mitotic spindle
What is the centrosome
An organelle near the nucleus of a cell which contains the centrioles, and from which the spindle fibres develop in cell division
What are the two centrioles referred to as, which one is which (think of their arrangement)
The mother and daughter, mother is the top of the T
What do the centrioles orchestrate
The microtubule network to orchestrate cell division
What are the nucleating sites of the centrosomes made of
Gamma-tubulin ring complexes
What needs to happen to the centrosome/centrioles for mitosis to occur
They need to duplicate
What happens in G1 to the centrosome
Separation of the mother and daughter centrioles
What happens after the mother and daughter centrioles separate and what phase does this occur during
They start to duplicate, the mother produces a daughter and vice versa, during S
What is nucleation
Putting microtubules together
Where are nucleating sites found (regarding centrioles)
In a cloud of protein complexes around the centrioles
Where do microtubules grow from
The nucleating points in the cloud of protein around the centrioles
What are the 6 phases of the cell cycle
Interphase, prophase, metaphase, anaphase, telophase, cytokinesis
What happens to DNA during prophase? Why? What is used to condense it
They condense to minimise DNA damage, histone proteins are used to wrap the DNA around
Describe how DNA is condensed
Short region of DNA double helix to beads on a string form of chromatin, to 30nm chromatin fibre of packed nucleosomes to an extended scaffold associated form to condensed scaffold associated form to condensed chromosomes
What difference to width of the chromosome from the with of a DNA double helix does condensation result in
2nm to 300nm which is wrapped to maker a super wide chromosome
What is the kinetichore fundamentally (molecule type and where)
Protein complexes that form at the centromere
What is the function of the kinetochore
To be a key regulator of processes around the chromosomes in the cell cycle
What are the 3 key events of prophase
Duplicated centrosomes migrate to opposite poles of the nucleus and replicated chromosomes condense and nuclear envelope begins to break down
By what point are there two centrosomes
Late prophase
What begins at the start of late prophase
The nuclear envelope breaks down
When does the nuclear envelope begin breaking down
Late prophase
What happens as the nuclear envelope breaks down
Centrosomes migrate to opposite sides of the cell
At what point do centrosomes migrate to opposite ends of the cells
Late prophase
What do the centrosomes begin to do when they reach opposite sides of the cell
Organise the spindle
What are ASTERS
Radial microtubule arrays
What are radial microtubule arrays also knows as
ASTERS
What do radial microtubule arrays/ASTERS form around
MTOC (microtubule organising centre)
When do radial arrays/ASTERS begin to form
Late prophase
What are radial arrays/ASTERS called when they join spindle fibres
Polar microtubules
Are microtubules/spindle fibres static structures
No, they are constantly polymerising and depolymerising and being turned over
What happens during early prometaphase (3)
Breakdown of nuclear membrane
Spindle formation
Attachment of chromosomes to spindle via kinetochores (centromere region of chromosome)
Where on the chromosome do spindle fibres attach
The kinetochores
What happens during late prometaphase (3)
Microtubule from opposite pole is captured by its sister kinetochore
Chromosomes attached to each pole congress to the middle
Chromosome slides rapidly towards centre along microtubules for alignment to occur
What 2 proteins in the kinetochore senses the attachment of microtubules
CENP-E
BUB protein kinase
What is CENP-E and its function
A protein in the kinetochore which senses the attachment of microtubules
What are the three types of half spindle and where do they bind
Kinetochore microtubule - bound to the kinetochore
Polar microtubule - A microtubule that has met and connected with a microtubule from the other centrosome
Astral microtubule - microtubule that is originating from the centrosome that does not connect to a kinetochore
What holds sister chromatids together
Cohesin
When do paired chromatids separate
During anaphase
What happens during anaphase A (3)
Cohesin breaks down
Microtubules get shorter
Daughter chromosomes pulled towards opposite spindle poles
When does cohesin break down
Anaphase A
What happens during anaphase B (2)
Daughter chromosomes migrate towards poles by the spindle fibres breaking down and becoming shorter Spindle poles (centrosomes) migrate apart
What happens during telophase
Daughter chromosomes arrive at each pole
Nuclear envelope reassembles at each pole
Cells try to revert to their normal size
What is a contractile ring made of
Actin and myosin
How does the cell cleave into two
The contractile ring squeezes the cell so that it divides into two daughter cells
What is a cleavage furrow
Where two cells are going to be cleaved during cytokinesis
What is the midbody of cytokinesis
Where the actin myosin contractile ring forms
When is the spindle assembly checkpoint/mitotic checkpoint
When the cell wants to exit metaphase and enter anaphase (a.k.a. the anaphase checkpoint)
What inhibits CENP-E from making a signal
Microtubule attachment
What protein dissociates from the kinetochore when chromatids are properly attached
BUB protein kinase
What is the function of BUB protein kinase
To dissociate from the kinetochore when microtubules attach to the kinetochore, this then signals the cell to tell it to proceed into anaphase
How can you get aneuploidy
If anaphase initiates before the spindle fibres attach/attach properly
What are the four types of misattachment of microtubules called
Syntelic, amphelic, monotelic and merotelic
What is syntelic attachment
Both kinetochores are hooked from microtubule arrays from the same centrosome
What is amphelic attachment
Normal microtubule attachment to the kinetochore
What is merotelic attachment
When 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 monotelic attachment
When only one of the kinetochores of one chromatid is attached to a microtubule array, the other kinetochore is unattached
What is normal microtubule attachment to the kinetochore known as
Amphelic attachment
What is it called when only one of the kinetochores of one chromatid is attached to a microtubule array, the other kinetochore is unattached
Monotelic attachment
What is it called when more than one microtubule array attached to the same kinetochore - meaning that one of the chromatids is being pulled in two different directions
Merotelic attachment
What is it called when both the kinetochores are hooked by two microtubule arrays from the SAME centrosome
Syntelic attachment
What does merotelic attachment result in
Loss of the chromosome at cytokinesis
What does syntelic attachment and monotelic attachment result in
Both sister chromatids at the same pole
What type of microtubule attachment results in a loss of a chromatid at cytokinesis
Merotelic
What are the three roads to aneuploidy
Mitotic checkpoint defect
Misattachment of microtubules to kinetochores
Aberrant cytokinesis
How can you get aberrant mitosis (think of centromere duplication)
Centromeres that aren’t duplicated properly could mean you have 4 centrosomes in one cell, or 1 centrosome doesn’t form a spindle properly or something so you end up with more chromatids in one cell and none in another
What can exploiting checkpoint control mechanisms achieve
Inhibition of the proliferation of a tumour
What holds cells in G2 until all is ready to proceed into mitosis
CHKE1 and CHKE2 (serine threonine kinase)
What do taxanes and vinca alkaloids do (3) and what cancers are they used for (2)
Alter microtubule dynamics
Produces unattached kinetochores
Causes long-term mitotic arrest
Breast and ovarian
What does CENP-E inhibition do
Cause the cell to think it has correctly hooked onto microtubules and proceed into anaphase
What happens if something goes wrong during the cell cycle? (2)
Cell cycle arrest at checkpoints to try fix problem
Apoptosis if problémo is too big
What stimulates cell division
Growth factors
When is the first cell checkpoint
G1
What can tumours do to the G1 checkpoint
Hijack it and stimulate excessive cell division
How many cell cycle checkpoints do we need to know of and where are they
3, near the end of G1, just before mitosis and the anaphase/mitotic/spindle assembly checkpoint between metaphase and anaphase
What can tumours do to the second checkpoint
Block the sensing of DNA damage and cause the cell to continue with mitosis
What is the purpose of the second checkpoint
To check for DNA damage before entering mitosis
What is the third checkpoint and what does it do
The metaphase/anaphase checkpoint and it checks that microtubules are attached to kinetochores correctly
What do tumours do to the third checkpoint
Completely bypass the metaphase/anaphase checkpoint (a.k.a. the mitosis/spindle assembly checkpoint)
What can tumours block the ability of a cell to do regarding G0
Tumours block the ability of the cell cycle to enter G0, go straight from cell cycle to cell cycle
What does a cell need to leave G0
Growth factors triggering intracellular signalling cascades
What triggers a signalling cascade
Extracellular factors binding to receptors and activating them
What happens to the signal generated by a signalling cascade as it travels
It is relayed, amplified and integrated and then is diverted to multiple targets
Give two examples of peptide growth factors
Epidermal growth factor (EGF) and platelet derived growth factor (PDGF)
Explain growth factor ligand receptor binding, state of receptor included
Receptors are usually found in the monomeric, inactive state.
When a ligand binds to the EC domain of the monomeric receptor, the receptors come closer and form dimers by activating the kinase domain. The kinase domain phosphorylates one another to activate the receptor.
What are growth factor receptors known as
Receptor protein tyrosine kinase
What type of protein mediates amino acid acid phosphorylation
Kinases
What is the ‘activation trigger’
Phosphorylation of a protein
How can phosphorylation of a protein be reversed
Protein phosphatases
What are the two types of protein kinase
Serine and tyrosine
What are the three amino acids that can be phosphorylated
Serine, threonine and tyrosine
Which type of kinase can phosphorylate 2 amino acids and which 2 amino acids?
Serine kinase - serine and threonine
What charge is on a phosphate group
-ve
How can a phosphate group alter protein function (2)
Cause a change in shape (conformation)
Creating a docking site for another protein
What does growth factor receptor activation and dimerisation trigger (2)
Kinase cascades
Binding of adaptor proteins
What protein does a kinase often regulate? What does this allow (3) and what is the benefit of this?
Another kinase. Signal amplification, diversification and opportunity for regulation. Multiple steps allows more control and to fix mistakes
What reverses phosphorylation
Phosphatases
