Cell Replication Flashcards
What is the cell cycle?
An orderly sequence of events in which the cell duplicates its contents and divides in two
What stages of the cell cycle make up interphase?
G1 + S + G2
What factors do different rates of mitosis depend on?
- How complex the system is
- The need for renewal
- Age
- Tumour = out of sync replication
- State of differentiation as some cells never divide
Which cells never divide?
Neurons and cardiac myocytes
What does pre-mature, abnormal mitosis result in?
Cell death
Why is mitosis the most vulnerable period of the cell cycle?
DNA damage cannot be repaired, gene transcription is silenced, cell metabolism is low, cells are killed more easily
What is G0?
The quiescent phase
What state are the cells in when they are in G0?
The cells are not dormant, but non-dividing
What does the centrosome consist of?
Two centrioles at 90 degrees to one another
What is a centriole?
Barrels of 9 triplet microtubules which form the mitotic spindle
Where do the microtubules grow from on the centrosome?
Microtubules grow from the nucleating site on the centrosome
Microtubules are polymers of what?
Alpha and beta tubulin dimers
What is a kinetochore?
Protein complexes that assemble at the centromere of a chromosome and function to connect the chromosome to the microtubules during anaphase
In what phase of mitosis does the spindle attach to the kinetochore?
During metaphase
What happens to the microtubules during anaphase?
They get shorter as they pull chromosomes apart
In which phase d the spindle microtubules start to form?
Prophase
What occurs in the G1 phase of the cell cycle?
The cell makes mRNA and proteins in preparation for the next steps
What is aneuploidy?
An abnormal number of chromosomes
What is meant by syntelic attachment of the spindle?
When both kinetochores attach to spindle from one spindle pole, so the whole chromosome is pulled to one pole
What is meant by merotelic attachment?
When spindle from two poles attach to one kinetochore
What occurs during the S phase?
The synthesis phase - organelle replication and protein synthesis
What happens during the G2 phase?
Period of rapid cell growth in preparation for mitosis
What happens to cohesin during anaphase?
Cohesin breaks down
What occurs during the telophase?
The daughter chromosomes arrive at the spindle and nuclear envelopes reassemble at each pore
What happens to chromatin during the prophase?
Chromatin condenses
What is the function of a MTOC?
Microtubule Organising Center - forms the spindle fibers
How do we get cell growth? (Leaving G0 to G1)
Growth factors bind to tyrosine kinase receptors, which triggers an intracellular signalling pathway which ultimately leads to protein synthesis increasing and protein degradation decreasing, stimulating cell growth
What type of molecule is c-Myc?
A transcription factor
What does c-Myc promote?
G0 to G1 transition
Which oncogene is over expressed in many tumours?
c-Myc
what two things can occur if something goes wrong with cel replication?
- Cell cycle arrest - can be temporary while damage is being fixed
- Programmed cell death = apoptosis
What happens to the cell when the DNA damage is too great and cannot be repaired?
Programmed cell death = apoptosis
In the absence of a stimuli to progress into the next stage of replication, what happens to the cell?
Cells go into G0 phase (quiscent phase)
What does the exit from G0 phase require?
Growth factors and intracellular signalling cascades
What forms when cyclins bind to cyclin dependant kinases?
They form an activated cyclin-CDK complex
What do cyclin dependant kinases have to bind to in order to be activated?
Cyclins
Which Cdk’s and cyclins mediate the transition from G1 to S phase?
Cdk2-Cyclin E complex
Which Cdk’s and cyclins mediate the transition from S to G2 phase?
Cdk2-Cyclin A
How are cyclins expressed through the cell cycle?
expressed transiently
How are cyclins switched off during the cell cycle?
They are made inactive by ubiquitination - this is where tags are added to destroy the cyclin
Describe how Cyclin E helps the cell move from G1 to S phase
Cyclin E -> Binds to Cdk2 -> a lot of complexes are formed -> This leads to the phosphorylation of Rb -> Means Rb releases E2F transcription factor, so cell can continue to proliferate
How does retinoblastoma protein work?
It holds an inactive E2F transcription factor and only releases it when Rb is phosphorylated
What phosphorylates Rb?
Activated cdk-cyclin complexes
Describe how p53 works as a tumour suppressor?
- p53 recognises damage to DNA
- p53 phosphorylated = activated
- Active p53 binds to p21 gene
- Makes p21 protein
- p21 is a cdk inhibitor so no cdk complexes can form to phosphorlyate Rb so no progression into next phase
What does p21 do?
it inactivates Cdk-cyclin complexes meaning they cannot go and phosphorylate Rb
When does Cdk activity peak?
During mitosis
Why are cyclins given their name?
They are produce and then degraded throughout the cell cycle
What does c-Myc induce the expression of?
Cyclin D
Why is cyclin D so important?
entry to the cell cycle requires Cyclin D
what two checkpoints can occur in the G1 phase?
Checks for damaged DNA and unfavourable extracellular environments
What checkpoints can occur in the S phase?
Damaged or incompletely replicated DNA is search for
What can induce a checkpoint in mitosis phase?
Chromosome improperly attached to the mitotic spindle
What do protein kinase cascades lead to?
Signal amplification, diversification and an opportunity for regulation
Why are protein kinases useful for cell cycles?
Since the protein kinases can be turned on and off, it is very helpful in regulating the progression through the cell cycle
What actually activates Cdks?
After cyclin has bound, the Cdk complex has to be sequentially phosphorylated with inhibitory and activating phosphates. Once the inhibitory phosphate has been removed by protein kinases, the complex is active
What removes inhibitory phosphates from the Cdk complexes in order to make it inactive?
Phosphatase
How does positive feedback in the Cdk-cyclin system work?
The active Cdk complexes then activate more phosphatases so the inhibitory phosphates can be removed from the inactive complexes, leading to more activation of complexes
During ubiquitination, what do cyclins get degraded into?
Amino acids
How might over expression of c-Myc lead to aberrant cell cycling and cancer?
Inappropriate entry into G1 – S phase
How are Cdks rendered active to allow progression to the next phase of the cell cycle?
- Binding of cyclins
- Phosphorylation
- Dephosphorylation
How are active Cdk-cyclin complexes rendered inactive to allow orderly progression to the next phase of the cell cycle?
Degradation of cyclins
How can p53 rapidly respond to DNA damage?
p53 protein is continuously made and degraded
