Cell Replication Flashcards
What is the Cell Cycle?
Orderly sequence of events in which the cell duplicates and divides in 2
What are the three stages of the cell cycle?
Duplication
Division
Co-ordination
Why may different cells divide at different rates?
Adult vs Embryonic cells
Complexity of system
Necessity for renewal
State of differentiation
Which phases make up Interphase?
G1
S (DNA replication)
G2
What is the M phase?
Mitosis (nuclear division)
Cytokinesis (cytoplasmic division)
What is the quiescent phase?
Inactive stage that occurs when cell leaves the cell cycle (after Mitosis). May stay in this phase until it is triggered externally to enter G1.
Why might a cell pause during cell cycle?
DNA repair
undergoes apoptosis if mistakes in DNA are too much to repair.
What is c-Myc?
Transcription factor-stimulates expression of cell cycle genes.
Oncogene-overexpressed in many tumours.
How might cells leave G0?
Response to extracellular growth factors
Signal amplification
Signal integration by other pathways
Ras/Raf/MEK/ERK- increase protein synthesis and decrease protein degradation leading to cell growth
What oncogene causes progression of cell from G0 to S phase and how does it do this?
c-Myc
Increases the concentration of Cyclin D
What is the purpose of Cdk (cyclin dependent kinases)
Phosphorylation at serine/threonine/tyrosine
Where are Cdks found?
All proliferating cells
When are Cdks active?
ONLY when bound to cyclin
What allows progression into the S phase?
when cyclin 4/6 are bound to cyclin D
What is progeny?
Daughter cells that carry genetic defects
What effect does phosphorylation have on kinases?
Activates them
What effects does phosphatases have on kinases?
Turns them off by dephosphorylation
How are Cdks activated?
Cyclin produced and binds to Cdk
Phosphorylation of Cdk-cyclin complex at inhibitory and activating sites of Cdk
Phosphatases remove inhibitory phosphate from Cdk, activating it
How does positive feedback act to increase the amount of active Cdk?
Activated Cdk activates more of the phosphatase to remove more inhibitory phosphates from Cdk-cyclin complexes
Explain the process by which Cyclins are turned off
Cyclin is ubiquitylated (tagged)
Leading to destruction of cyclin
Therefore Cdk is inactive
Which Cyclin-Cdk complex leads to progression into S phase?
Cyclin S- Cdk complex
Which Cyclin-Cdk complex leads to progression into the M phase?
Cyclone M- Cdk complex
How are specific direction and timing given to the cell cycle?
Cdks become sequentially active and stimulate synthesis of genes required for the next phase
How does the activity of the cyclins allow the cell cycle to be cyclical?
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 pathways lead to production of activated Cdk
activated Cdk phosphorylates the Retinoblastoma that is bound to TF, inactivating it
This causes Retinoblastoma to release TF, targeting activation of genes such as DNA polymerase and thymidine kinase
What is the function of p53?
They 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
binds to and activates transcription and translation of p21
enzyme formed from expression of p21 inhibits action of Cyclin-cdk complex
Stops cell cycle from continuing
