cell replication Flashcards
- What are the stages of the cell cycle?
Duplication
Division Co-ordination
what factors affect the time take for cells to divide
Embryonic VS adult cells
complexity of system eg for yeast cells, only 1.5- 3 hours
Necessity for renewal eg intestinal epithelial 20hrs, hepatocytes is once per yr
- Which phases make up Interphase?
- What is the M phase?
- What is the quiescent phase?
G1
S (DNA replication)
G2
Mitosis (nuclear division) and cytokinesis
Inactive stage that occurs when the cell leaves the cell cycle- G0
It may stay in this phase until it is triggered externally to initiate G1 phase
What are the checkpoints in cell cycle?
- G1-S checkpoint
- G2-M checkpoint
- during M phase
- during G1 phase
check if enough nutrients/ growth factors
check if DNA is abnormal/ replicated incorrectly
if it is, DNA repair
if not, undergo apoptosis
if chromosomes are properly attached to spindle
if DNA is damaged
- How might cells leave G0?
Response to extracellular factors eg tyrosine kinase
growth factors signal cell to go from G0 to G1 phase
Signal amplification
Signal integration by other pathways
Ras/Raf/MEK/ERK (increase protein synthesis and decrease protein degradation)
leading to increased cell growth
- What is c-Myc?
- What oncogene causes progression of cell from G0 to S phase and how does it do this?
transcription factor - stimulates the expression of cell cycle genes
oncogene - over-expressed in many tumours
c-Myc Increases concentration of Cyclin D
- What is the purpose of Cyclin dependent kinase (Cdk)?
- Where are Cdks found?
- When are Cdks active?
Phosphorylation and dephosphorylation at serine/threonine/tyrosine
part of signalling events
All proliferating cells Only when bound to cyclin
why are CDKs only sequentially active?
what do CDK- cyclin complexes do?
as they are only active when bound to cyclin, and cyclin concentrations fluctuate within cycle
stimulate synthesis of genes required for next phase
gives direction and timing to cycle
which cyclin- Cdk complex drives cell into
- G0 to G1
- G1 to S
- S to G2
- G2 to M
- M to end of cell division
Growth factor induces expression of C-myc, driving cell into G1
C myc stimulates expression of Cyclin D, which binds to CDK 4/6
CyclinD-CDK4/6 complex stimulates expression of cyclin E, which binds to CDK2
Cyclin A and CDK2
Cyclin B and CDK 1
- What effect does phosphorylation have on kinases?
- What effects does phosphatases have on kinases?
Activates them
Turns them off (if removing an activating phosphatase)
- 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?
- Explain the process by which cyclins are turned off?
The activated Cdk activates more of the phosphatase to remove further inhibitory phosphates from Cdk-cyclin complexes
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?
- Which Cyclin-Cdk complex leads to the progression into M phase?
Cyclin S - Cdk Complex
Cyclin M - Cdk Complex
- How does the activity of the cyclins allow the cell cycle to be cyclical?
- What is Retinoblastoma?
The cyclins are susceptible to degradation, so they can be formed again
Tumour suppressor
- How is Retinoblastoma involved in cell proliferation?
Activation of intracellular signalling leads to production of activated Cdk
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
