Cell Cycle and its Control Flashcards
What are two cell types that do not divide?
Neurones and Cardiac Myocytes
What happens when Premature, abberant mitosis occurs?
Cell death
What changes in DNA are often seen in cancer cells?
Mutations in Oncogenes and tumour suppressor genes
Aneuploidies
Why do tumours tend to keep growing?
They lack contact inhibition of growth - don’t sense neighbour cells
Why is Mitosis the most vunerable point in the cell cycle?
Cells are more easily killed during mitosis which is why it takes such little time
When DNA is damaged during Mitosis, it cannot be repaired
What are the 5 main Stages of the cell cycle?
Mitosis
G0 - Cell cycle machinery dismantled
G1 - Gap Phase
S - Synthesis phase
G2 - Gap Phase
Where are most cells in the cell cycle?
G0
What happens in the S phase?
DNA replication
Protein synthesis
Replication of Organelles
What is the centrosome?
Where is it located?
What does it consist of?
What are its functions?
Organelle which contains Centrioles from which the spindle fibres develop in cell division
Located near nucleus
Consists of mother and daughter centrioles (barrels of nine triplet microtubules)
Acts as Microtubule organising centre and Mitotic spindle
Describe the process of Centrosome replication:
- G1: Seperation of the mother and daughter centrioles
- S: The start to duplicate (mother produces daughter, daughter produces mother)
What is nucleation?
The polymerisation of microtubule monomers to make a long filament
What happens in Centrosome nucleation?
There is a cloud of protein complexes around the centrosomes which are nucleating sites
As the cell encounters a need for mitosis the microtubules start to grow from these points to form an array of microtubules
(look like sea urchin)
What are the six phases of mitosis?
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis
What happens in Prophase?
Duplicated DNA condenses (to reduce damage during mitosis)
Late Prophase: Nuclear envelope breaks down
Centrosomes migrate to opposite sides and begin to organise the spindle
What is the order of DNA condensation?
- Double helices wrap around histones to form beads on a string form of chromatin (from 2nm to 11nm)
- string further wraps around itself (30nm)
- A chromosome scaffold then forms (300nm)
- Further wrapping until chromosome (700nm then 1400nm)
Describe the anatomy of a chromosome:
Each chromosome consists of two sister chromatids
The Centromere wraps around the chromatids like a belt
Protein complexes on the centromere form the Kinetochore
Describe spindle formation:
Radial microtubule arrays (ASTERS) form around each chromosome
The radial arrays meet in the middle
Polar microtubules are formed
These form highways telling the chromosomes where to go
What happens in early prometaphase?
Breakdown of nuclear envelope
Spindle formation is largely complete
Attachment of chromosomes to spindle via kinetochore
How do spindles connect to chromosomes?
Each microtubule meeting in the middle needs to find a chromosome
Spindles attach via the kinetochore
One microtubule array will attach to the kinetochore on one side and another will attach on the other side
There are specialised proteins in the kinetochore that sense the attachment of microtubules
What happens in Late Prometaphase?
The sister chromatids have been captured by the microtubule arrays
Once captured, the chromosomes slide rapidly towards the middle of the cell
What are the three types of half-spindle?
Kinetochore microtubule - Bound to the 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 does not connect to a kinetochore
What happens in Anaphase?
Anaphase A:
Cohesin - the protein complex that holds the sister chromatids together - breaks down
The microtubules begin to shorten and the chromatids move towards the centrosomes
Anaphase B:
The daughter chromosomes reach the opposite poles - either by microtubule shortening or moving apart of centrosomes
What happens in Telophase?
Daughter Chromatids reach pole
Nuclear envelops reassemble
Contractile ring of actin and myosin filaments forms
The cleavage furrow is where the cells are going to be cleaved
What happens in Cytokinesis?
New membrane inserted at the cleavage furrow
Midbody is formed (Where the actin-myosin ring is formed)
Actin-Myosin ring contracts - Cytokinesis
When is the Spindle Assembly Checkpoint?
After Metaphase before Anaphase can commence
What does the Spindle Assembly checkpoint ensure?
Completion of Chromosome Alignment
Checks for Spindle Assembly
How does the Spindle assembly checkpoint work?
Kinetochores emit a signal when the kinetochore is not attached to microtubules
When all kinetochores have microtubules bound, the signals have all stopped and anaphase can commence
What are two proteins that are involved in the Spindle Assembly Checkpoint?
CENP-E
BUB Protein Kinase
BUBs dissociate from the Kinetochore when the chromatids are properly attached to the spindle - They then go on to signal progression to anaphase
What happens if anaphase initiates before the Spindle Assembly Checkpoint?
(Mitotic Checkpoint Defect)
Before all the microtubules have attached, if Anaphase initiates, there will be an abnormal division of the chromosomes between the daughter cells
This results in Aneuploidy
What are the three ways Misattachement of Microtubules to Kinetochores may occur?
(Just the names)
Syntelic Attachment
Merotelic Attachment
Monotelic Attachment
What is Syntelic Attachment?
Both 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
- One of the sister chromatids is being pulled in two directions
What is Monotelic Attachment?
Only one of the kinetochores of one chromosome is attached to a microtubule array, the other is unattached
What happens at cytokinesis if there has been a Merotelic attachement?
Chromosome loss from one of the daughter cells at cytokinesis
What is aberrant Mitosis?
If the centrosomes are not duplicated properly, you could end up with 4 centrosomes in one cell
This leads to very abnormal attachment of microtubules to the kinetochores leading to abnormal cytokinesis producing 4 cells
How can an anti-cancer therapy be used to exploit the Mitotic checkpoint?
(What types of chemotherapeutics are used and for which cancers?)
Taxanes and Vinca Alkaloids (Breast and Ovarian)
By inhibiting the checkpoint, you can cause the cell to proceed to anaphase before all the chromatids are attached to microtubule arrays.
By altering microtubule dynamics, long-term mitotic arrest is caused
These are more easily killed
What happens if DNA damage is detected during the cell cycle?
If repairable then cell cycle is arrested whilst it is repaired
If irreversible, then apoptosis
Where are the three main checkpoints during the cell cycle?
During G1
Before Mitosis (End of G2)
Metaphase-Anaphase checkpoint
What causes cell division?
Exit from G0 requires growth factors and intracellular signalling cascades
What is deregulation of the cell cycle during tumorigenesis?
Normally when cells exit G1 they enter G0
Tumours block the ability of the cell to enter G0; they continue to divide - cell cycle apparatus is not dismantled
