L20 yeast as a model in human disease

Question 1

what are cell models to understand cell defects ?

Answer 1

yeast Saccaromyces cerevisiae and Schizosaccharomyces pombe

Question 2

what are the advantages of using yeast?

Answer 2

1. the genome sequences for both yeast are available
2. easy to delete genes
3. unicellular and grow in defined media
4. both have a haploid AND diploid life cycle useful for genetics
5. fundamental processes are conserved in eukaryotes

Question 3

what does cyclin dependant kinase (CDK) do?

Answer 3

Cdc28 interacts with phase-specific cyclins in Saccharomyces cerevisiae
binding to CDKs and providing substrate specificity during the cell cycle.

Question 4

Checkpoint G1 phase

Answer 4

IN MAMMALS: - restriction point - growth factor control
IN YEAST: - Start point - nutrients in yeast
cell size control

Question 5

Checkpoint G2-M phase

Answer 5

Ensures DNA replication is complete
cell is big enough
good environment

Question 6

M phase checkpoint

Answer 6

Ensures correct spindle attachment

triggers chromatid separation

Question 7

G0 phase checkpoint

Answer 7

cell exits the cell cycle

Question 8

how is cancer a disease of the cell division cycle?

Answer 8

1. several independent mutations are required
2. the spontaneous mutation rate cannot account for the incidence of cancer in population
3. environmental factors affect the rate of damage accumulation
4. mutations of the cell cycle checkpoints

Question 9

how many genes in Schizosaccharomyces pombe are involved in cancer?

Answer 9

the yeast has appx 5000 genes

141 genes associated with cancer from all sources

Question 10

Examples of cancer linked genes found in Saccharomyces cerevisiae?

Answer 10

1. DNA repair gene- MSH2
   - in humans associated with hereditary non-polyposis colon cancer
   - the yeast has a gene with very high homology to MSH2
   - in yeast it is involved in DNA repair

Question 11

Examples of cancer linked genes found in Saccharomyces cerevisiae?

Answer 11

2. Cell cycle checkpoint gene - ATM
   - human patients exhibit increased sensitivity to ionising radiation and are >100 times more likely to develop cancer
   - the yeast has 2 genes with very high homology to ATM (MEC1 and TEL1)
   - in yeast these genes encode a protein kinase
   - involved in cell cycle checkpoint control with response to DNA damage

Question 12

how is yeast used in human disease?

Answer 12

1. as a model system to identify new anti-cancer targets for new clinical approaches specifically to kill cancer cells
2. synthetic lethal screens for lethal pairwise combinations of gene mutations

Question 13

how is the yeast involved in human disease?

Answer 13

appx 6-7% of the 5000 genes include “disease associated” indicating the info will provide insight to human diseases