Lecture 28

Question 1

Metaphase checkpoint:

Answer 1

• The spindle assembly checkpoint
• Is everything ok at metaphase? If so, anaphase can ensue - the division of chromosomes down the spindles
• If the kinase activity is inhibited there will be a pause in the cell cycle to give the chromosomes a chance to correct themselves

Question 2

APC/C

Answer 2

• Anaphase promoting complex
• Results in the destruction of cyclins and CDK targets become de-phosphorylated
• Mitosis is complete and cells enter G1
• Inactive APC/C and activating subunit (cdc20) form a complex
• Cdk and M-cyclin join up
• Ubiquitylation dependent degradation of the M-cyclin
• The M-cyclin in the proteasome is degraded

Question 3

Proteins involved in the cell cycle:

Answer 3

• Protein kinases and protein phosphatases that modify Cdks
• Cdk inhibitor proteins (CKIs)
• Ubiquitin ligases and their activators

Question 4

Cdks through the cell cycle:

Answer 4

• G1: G1-Cdk (favourable extracellular environment), Gs/S-Cdk -> S- Cdk (DNA damage)
• S: S-Cdk (DNA damage)
• G2: M-Cdk
• M: APC/C

Question 5

The p53 gene:

Answer 5

• Tumour suppressor genes control the cell cycle, loss of p53 activity results in uncontrolled division

Question 6

The myc gene:

Answer 6

• Oncogenes promote cell division
• When overreactive there is uncontrolled division
• Myc is a oncogene
• Some tumour viruses encode oncogenes which promote uncontrolled division

Question 7

Tumour suppressor genes vs Oncogenes:

Answer 7

• Two copies of tumour suppressor genes
• Two copies of proto-onco genes
• This results in normal cell division
• If the tumour suppressor genes are mutated, uncontrolled cell growth will occur and excessive cell proliferation follows
• If both of these are mutated there will be excessive cell proliferation
• Mutations lead to cancer, and this occurs more frequently as we age

Question 8

p53 knockout in mice:

Answer 8

• Heterozygotes and heterozygotes generated
• Mice deficient for p53 are prone to developing cancers
• Double knockouts died really quickly, heterozygotes died more quickly than p53 homos

Question 9

Myc over expression in fish:

Answer 9

• Over expression of the myc oncogene causes tumours in fish

Question 10

Animals cells and the Rb effect:

Answer 10

• Mitogen stimulates the cell cyle
• The Transmembrane receptor signals RAS (an oncogene)
• Signals a MAP-kinase pathway
• Signals a regulatory gene into the nucleus
• Myc responds by activating further genes
• G1-cdk is produced and the cell cycle continues
  Rb: retinoblastoma protein can stop the cell cycle acting normally (but this can be blocked by phosphorylation)

Question 11

p53 and DNA damage:

Answer 11

• p53 phosphorylation can block the cell cycle, so there is a chance to repair DNA damage
• p53 blocks the cell cycle if there is excessive stimulation of cell proliferation by an oncogene
• Excessive Myc production can result in p53 opposition
• If p53 is damaged, you can’t pause so cells proliferate! CANCERS!

Question 12

Through the lineage of mitotic cell divisions a number of mutagens are encountered:

Answer 12

• Intrinsic mutation processes
• Environmental and lifestyle exposures
• Mutator phenotype
• Chemotherapy
• The accumulation of mutations lead to a negative effect long term

Question 13

Cool fact:

Answer 13

• There are more cancer cells in 10 grams of tumour than there are people on earth! WOW!