Lecture 28 Flashcards Preview

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Flashcards in Lecture 28 Deck (13):

Metaphase checkpoint:

- 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



- 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


Proteins involved in the cell cycle:

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


Cdks through the cell cycle:

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


The p53 gene:

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


The myc gene:

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


Tumour suppressor genes vs Oncogenes:

- 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


p53 knockout in mice:

- 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


Myc over expression in fish:

- Over expression of the myc oncogene causes tumours in fish


Animals cells and the Rb effect:

- 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)


p53 and DNA damage:

- 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!


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

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


Cool fact:

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