Tumours 4 Flashcards
What is the order of the cell cycle starting from M?
M, G1, S, G2 and back to M
Which parts of the cell cycle make up the interphase (longest part)?
G1, S, G2
What is G0?
Resting mode of the cell
what process in the cell cycle ensures each cell receives a full chromosome complement and does not have any mutations?
Quality control check
What can be the outcomes if there is a problem with the cell and it doesn’t pass the quality control? (2)
- DNA is fixed/ repaired
2. apoptosis occurs
what are some external factors which affect cell cycle control?
- hormones
- growth factors
- cytokines
- stroma (connective tissue cells)
What intrinsic factors can affect cell cycle control?
- critical checkpoints (restriction point)
- after restriction point, progression becomes autonomous (cell controls itself)
what occurs in G1 phase? (2)
- cell increases in size
- G1 checkpoint ensures everything is ready for DNA synthesis
what occurs in S phase?
DNA replication occurs
What occurs in G2 phase? (2)
- cell continues to grow
- checkpoint ensures that everything is ready to enter the M phase
what chemicals are present at checkpoints?
cyclically active and inactive enzymes
What are catalytic subunits activated by?
Regulatory subunits
What are catalytic subunits called?
Cyclin-dependent kinases (CDKs)
what are regulatory sub-units called?
Cyclins
What is the active enzyme complex called in the cell cycle?
CDK/cyclin complex
What do active CDK/cyclin complexes do?
Phosphorylate proteins (which results in activation or inactivation of substrates)
What form are CDKs constitutively expressed in?
Inactive form
What does CDK need to become activated?
Cyclins
what kind of phosphorylation occurs at pRb?
hypophosphorylation
what happens to phosphorylation as cell progresses through the cycle?
increases
what phosphorylates pRb?
active cyclin D/CDK complexes
What happens to the cell cycle when it stops? (in terms of pRb and E2F)
- pRb is active (hypophosphorylated)
- inactive E2F
What happens to the cell cycle when it goes ahead? (in terms of pRb and E2F)
- inactive pRb ( phosphorylated)
- active E2F
What activates vital target genes in the cell cycle?
free E2F transcription factor
What is the E2F factor?
Stimulator of cell cycle entry
What does active pRb do to the cell cycle?
Puts a brake on the cell cycle (stops it)
What 3 factors are affected which cause a cell to lose control of its proliferation?
- cell division
- apoptosis
- DNA repair
What 3 non-lethal genetic damage can cause carcinogenesis?
- chemicals
- radiation
- oncogenic viruses
what does chemical carcinogenesis cause in DNA on a molecular level?
purine and pyrimidine bases in DNA are critically damaged by various oxidising and alkylating agents
What is formed as a result of chemical carcinogenesis on particular chromosome sites?
Adduct formation (DNA adducts)
What does radiation carcinogenesis cause in DNA on a molecules level?
purine and pyrimidine bases in DNA are critical cellular targets for radiation damage
What are 3 examples of harmful radiation?
- UV present in sunlight
- X rays
- gamma radiation
what are the 2 regulatory pathways which are frequently disrupted?
- cyclin D-pRB-E2F pathway (absent or inactive pRb releases cell cycle brake and E2F is activated which causes proliferation)
- p.53 pathway (which is a tumour suppressor)
What does p.53 do?
tumour suppressor
What are the 4 genes which often have mutations causing cancers?
- Rb
- CDK4
- cyclin D
- p.16 (tumour suppressor gene)
What happens to the level of p.53 in damaged cells?
increases
Why is p.53 increased in damaged cells?
- facilitates DNA repair
- induces cell cycle arrest at G1 and apoptosis
What happens if there is a mutation to p.53 gene?
- cells do not arrest at G1 or repair damaged DNA
- cells proliferate and form malignant neoplasm (uncontrollable cell division)
