Cell replication Flashcards
What are the three basic sequence of events in the cell cycle?
Duplication
Division
Co-ordination
Which phases make up Interphase?
G1
S (DNA replication)
G2
What is the M phase?
Mitosis (nuclear division) and cytokinesis
What is the quiescent phase?
Inactive stage that occurs when the cell leaves the cell cycle
It may stay in this phase until it is triggered externally to initiate G1 phase
- Why might a cell pause during cell cycle?
DNA repair
Undergo apoptosis if mistakes in DNA replication are too much to repair
What is c-Myc?
transcription factor - stimulates the expression of cell cycle genes
oncogene - over-expressed in many tumours
How might cells leave G0?
Response to extracellular factors - growth factors
Signal amplification
Signal integration by other pathways
Ras/Raf/MEK/ERK (increase protein synthesis and decrease protein degradation leading to increased cell growth)
What oncogene causes progression of cell from G0 to G1 phase and how does it do this?
c-Myc
Increases concentration of Cyclin D
What is the purpose of Cyclin dependent kinase (Cdk)?
Control of key signalling events
Phosphorylation and dephosphorylation at serine/threonine
When are Cdks active?
Only when bound to cyclin
What allows progression into the S phase?
Cdk 4/6 binding to cyclin D
What is progeny?
Daughter cells that carry genetic defects
What effects does phosphatases have on kinases?
Turn them off
How are Cdks activated?
Cyclin produced and binds to Cdk
Phosphorylation of Cdk-cyclin complex at inhibitory and activating sites of Cdk
Phosphatase removes inhibitory phosphate from Cdk, activating it
How does positive feedback work to increase the amount of active Cdk?
The activated Cdk activates more of the phosphatase to remove further inhibitory phosphates from Cdk-cyclin complexes
Explain the process by which Cdks are turned off?
Cyclin is ubiquitylated (tagged)
Leading to destruction of cyclin
And so Cdk is inactive
Which Cyclin-Cdk complex leads to the progression into S phase?
Cyclin S - Cdk Complex
CDK2- Cyclin E
Which Cyclin-Cdk complex leads to the progression into M phase?
Cyclone M - Cdk Complex
How are specific direction and timing given to the cell cycle?
Cdks become sequentially active and stimulate the synthesis of genes required for next phase
How does the activity of the cyclins allow the cell cycle to be cyclical?
The cyclins are susceptible to degradation, so they can be formed again
What is Retinoblastoma?
Tumour suppressor
How is Retinoblastoma involved in cell proliferation?
Activation of intracellular signalling leads to production of activated Cdk complexes
They phosphorylate the active Retinoblastoma that is bound to the TF, inactivating it
This causes the Retinoblastoma to release the TF which then targets activation of genes such as DNA polymerase and thymidine kinase
What is the function of p53?
Arrest cells with damaged DNA in G1
How does p53 act as a tumour suppressor?
When double stranded DNA damage occurs, p53 is not degraded
p53 is activated via phosphorylation
It binds to and activates the transcription and translation of p21
The enzyme formed by expression of p21 inhibits the action of the Cyclin-Cdk complex
So the cell cycle can no longer continue
At what five checkpoints can the cell be arrested?
Mid G1 - due to damaged DNA
End of G1 - due to unfavourable extracellular environment
End of S - damaged or incompletely replicated DNA
Mid G2 - damaged or incompletely replicated DNA
End of M - chromosome improperly attached to mitotic spindle
Which cyclins are present in the cell cycle?
Cyclin A, B, D and E
Which cyclin dependent kinases (CDKs) are present in the cell cycle?
CDK1, 2, 4, 6
Name some oncogenes.
EGFR/HER2 -breast cancer
Ras - many cancers
Cyclin D1 - 50% breast cancers
C-myc -many tumours
Which cyclins are raised at the end of G1 ?
CDK 4/6 so cyclin D
Which cyclins and CDK are raised from end of G1 to mid S ?
CDK2 - cyclin E
Which cyclins and CDK are raised from mid S to mid M?
CDK2- cyclin A
Which cyclins and CDK are raised during the M phase?
CDK1- cyclin B
What is the action of P53?
Stops cells with damaged DNA from progressing past G1 phase
