Cell Replication Flashcards
What is the cell cycle?
What are the 3 steps involved in the cell cycle?
The cell cycle is an orderly sequence of events in which a cell duplicates its contents and divides in two.
Processes involved in the cell cycle:
-duplication - cell growth and chromosome replication
- division - chromosome segregation
- co-ordination - cell division
What factors does the rate of cell division depend on?
What are some types of cells that never divide?
- embryonic vs adult cells
- complexity of system
- necessity for renewal (intestinal epithelial cells ~20h, hepatocytes ~1 year)
- state of differentiation (some cells never divide - neurones & cardiac myocytes)
- tumour cells
What are the different phases of the cell cycle and what occurs during each phase?
What is interphase?
Cell cycle:
- G0 phase
1. G1 phase
2. S phase - DNA replication + replication of organelles esp mit, to provide energy for mitosis
3. G2 phase
3. M phase - mitosis (nuclear division) + cytokenesis (cytoplasmic division)
Interphase = G1 + S + G2
M phase = mitosis
What is the G0 phase?
G0 phase is where cells are not dormant but they are non dividing eg neurones, skeletal muscle, hepatocytes
In the absence of a stimulus most cells go into G0, most cells are differentiated to perform their specific functions.
When are the cell cycle checkpoints and what do they monitor?
What checkpoints can arrest the cell cycle?
Cell cycle checkpoints monitor external environment:
- nutrients
- growth factors
Pause cell cycle for:
- DNA repair
- undergo apoptosis
S phase checkpoint - is environment favourable?
G2 checkpoint - is all DNA replicated, is all DNA damage repaired?
M phase checkpoint - are all chromosomes properly attached to the mitotic spindle?
G1 - damaged DNA, unfavourable extracellular environment
S - damaged or incompletely replicated DNA
G2 - damaged or incompletely replicated DNA
How and why do cells ever leave the G 0 phase?
Cells leave the G 0 phase due to signalling cascades:
- response to extracellular factors: growth factors stimulate entry from G 0 into the G1 phase
- signal amplification
- signal integration/ modulation by other pathways
- Ras/RAF/MEK/ERK
Detail the steps involved in the cell growth pathway
Growth factor —> binds to growth factor receptor —> intracellular signalling pathway —> protein synthesis increased/protein degradation reduced —> cell growth
What is c-Myc, what does it do and when is it expressed?
c-Myc is a transcription factor - stimulates the expression of cell cycle genes
Growth factor signalling pathways induces the expression of c-Myc
- c-Myc promotes G0 to G1 transition
- c-Myc is an oncogene - overexpressed in many tumours
What are cyclin dependent kinases (Cdks)? What do they do?
What do they allow for? And where are Cdks present?
What is aetiology of the name cyclin?
Cyclin dependent kinases are involved in phosphorylation and dephosphorylation
- key signalling events
- serine/threonine/tyrosine
Cdks allow exquisite control of events:
- cdks present in proliferating cells
- BUT they’re only active when a cyclin is bound
Cyclins are named so bc their concs within the cell fluctuate. Cyclic production and degradation. Cyclin conc high during mitosis, only the cyclin:Cdk complex is active during mitosis.
What does entry into the cell cycle require?
What do protein kinase cascades lead to?
What type of enzymes is phosphorylation reversed by?
Growth factor -> C-Myc -> cyclin D -> cyclin D/Cdk 4/6 complex
Protein kinase cascade results in:
- signal amplification
- diversification
- opportunity for regulation
Phosphorylation is reversed by phosphatases
Cell cycle control is based on cyclically activated and expressed proteins.
When are cyclin dependent kinases present and what is their activity regulated by?
When are cyclins expressed in the cell cycle? How are they regulated?
Cdks: cdk1, Cdk2, CDK4, Cdk6
- present in proliferating cells throughout cell cycle
- activity of Cdks is regulated by: interaction w cyclins and phosphorylation
Cyclins: cyclinA, cyclinB, CyclinD, CyclinE
- Transiently expressed at specific points in the cell cycle
- regulated at level of expression
- synthesised, then degraded
How are Cdks activated? (3 steps)
How is control provided in the steps required to activate Cdks?
What drives the cell cycle forward?
What turns off cyclins? What are they degraded to?
What to Cdks stimulate the synthesis of?
What are cyclins susceptible to?
cdks are activated by sequential phosphorylation and dephosphorylation.
- Inactive cdk joins with a cyclin but remains inactive
- Kinases phosphorylate Cdk (there’s an inhibitory phosphate and activating phosphate site), cdk still inactive
- Phosphatases come and remove inhibitory phosphates, this activated Cdk
Each step can be regulated which provides control. Positive feedback drives the cell cycle forward: active M-Cdk activates the production of more active M-Cdks. Cyclins are turned off by ubiqutination -> cyclin degraded to amino acids.
Cdks become sequentially active and stimulate synthesis of genes required for next phase. Gives direction and timing to cycle.
Cyclins susceptible to degradation, hence cyclical activation.
What is a retinoblastoma(Rb)?
What does the cell cycle need in order to progress?
Retinoblastoma protein (Rb) - missing/inactive
- tumour suppressor
- abundant in all nucleated cells
For cell cycle to progress the cell needs to double in size -> via intracellular signalling pathways protein synthesis is increased
Rb acts as a brake on cell proliferation.
Describe the role of Rb in a resting cell and a proliferating cell
Resting cell - Rb acts as a break:
Active Rb sequesters a TF in an inactive form. The transcription factors can’t turn on genes needed for cell cycle progression.
Proliferating cell - Phosphorylation of Rb releases the brake:
- activation of intracellular signalling leads to production of G1-Cdk and G1/S-Cdk complexes
- they can phosphorylate Rb inducing the inactivation of Rb and release of the transcription factor
- target genes such as DNA polymerase and thymidine kinase are now activated.
What is the role of E2F?
What is the role of P53? How is it activated?
Release of E2F allows cell cell cycle progression, E2F family members regulate the expression of several genes needed for the cell cycle to progress.n
p53 arrests cells with damaged DNA in G1.
If DNA is damaged: protein kinases are activated that phosphorylate p53, stabilising and activating it -> active p53 binds to the the regulatory region of the p21 gene and it is transcribed-> p21 family members are inhibitors of cyclin:Cdk complexes -> cell cycle inhibited
In the absence of DNA damage, p53 is degraded in proteosomes
