Cell Replication Flashcards
What is the cell cycle
Duplication
Division
Coordination
Which phases make interphase
G1
S (DNA replication)
G2
What is the M phase
Mitosis and cytokineses
What is the quiescent phase
Inactive stage that occurs when cell leaves the cell cycle in absence of stimulus
Cell is non dividing not dormant
G0 is thus phase
Eg neurons skeletal muscles hepatocytes
Why might a cell pause during cell cycle
DNA repair
Undergo apoptosis if mistakes in DNA replication are too much to repair
How might cells leave G0
Response to extracellular factors eg growth factors
Signal amplification
Signal integration by other pathways
MAP kinases eg ras/raf/MEM/ERK
G1
Cell growth
Contains checkpoint which checks for damaged dna
G2
Preparation for mitosis
Checks for damaged or incompletely replicated DNA
Ras/RAF/MEK/REK
Increase protein synthesis
Inhibit protein degradation
Allows net growth of cell
C-Myc
Regulates cell cycle entry
Is an oncogene which is overexpressed in many tumors
C-Myc-transcription factor stimulates expression of cell cycle genes
Promotes G0 to G1
What oncogene causes progression of cell from G0 to G1 phase and how does it do this?
C-Myc
Increases concentration if cyclin D
- What is the purpose of Cyclin dependent kinase (Cdk)?
Phosphorylation and dephosphorylation of serine/threonine/tyrosine
Part of signallung events
Where are cdks found
In all proliferating cells
When are cdks active
Only when bound to cyclin
What allows progression into s phase
Cdk 4/6 binding to cyclin D
What effect does phosphorylation have on kinases
Activates them
What effects does phosphatases have on kinases?
Turns them off
How are cdks activated
Cyclin is produced and binds to cdk
Phosphorylation of Cdk-cyclin complex at inhibitory and activating sites of Cdk
Dephosphorylation by phosphatase which 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
How are cyclins turned off
Cyclin is ubiquitylated
Leads to destruction of cyclin
Cdk is inactive
Which Cyclin-Cdk complex leads to the progression into G1 phase
Cyclin D- Cdk4/6 Complex
Which Cyclin-Cdk complex leads to the progression into S phase
Cyclin E - Cdk2 Complex
Which Cyclin-Cdk complex leads to the progression into M phase?
Cyclin A - Cdk2 Complex
Which Cyclin-Cdk complex is formed after this?
Cyclin B - Cdk1 complex
How are specific timing and direction given to cell cycle
Cdks become sequentially active and stimulate synthesis of genes
How does the activity of cyclins allow the cell cycle to be cyclical
Cyclins are susceptible to degradation so they can be formed again
Cancers replication rate
Embryonic cells have a faster rate of replication
Tumor cells-excessivedysregulated cell replication
Retinoblastoma
Eye tumor suppressor
If rb protein missing or inactive there are issues with cell cycle progression
Rb acts as a brake in cell proliferation
What does rb do in a resting cell
Rb sequesters a transcription factor in an inactive form commonly E2F family
The TF can’t turn on genes needed for cell cycle progression eg dna polymerase and thymidine kinase
What does mitogen signalling do to rb in a proliferating cell
Activation of intracellular signalling through mitogens leads to production of G1-Cdk and G1/S-Cdk complexes
They phosphorylate the active Rb that is bound to TF, inactivating it which releases the TF
Target genes like DNA polymerase and thymidine kinase can now activate
What is the function of p53
They arrest cells with damaged dna in G1
P53
Recognizes double stranded breaks and activates kinases that phosphorylate p53
In absence of dna damage it is degraded
What happens when dna damage is detected
If dna damage is detected active p53 gene binds to regulatory region on p21 gene
Transcription of p21 and dna occur
P21 family members are inhibitors of cyclin/Cdk complexes
Loss of function mutation in over 50% of humans
Oncogenes
Ras-mutationally activated in cancers
Cyclin d1 over expressed in 50% of breast cancers
C-Myc overexpressed in many tumors
EGFR/HER2 mutationaly activated or over expressed in cancers
Tumor suppressors
Rb loss of function mutations in 80% of small cell lung cancers
P53 loss of function mutations in over 50% of cancers
How might over expression of c myc lead to aberrant cell cycling and cancer
Induces expression of cyclin D which drives inappropriate entry into G1-S phase
