L20: Yeast as a Human Disease Model

Question 1

Why is yeast a good model for human genetic disease?

Answer 1

The diseases are commonly associated with conserved fundamental processes such as the cell division cycle

Question 2

What are the advantages of using S.cerevisiae and S.pombe?

Answer 2

-Genome sequences are available
-Easy to delete genes
-Unicellular and grow in defined media
-Both have haploid and diploid life cycle
-Some fundamental processes are conserved in eukaryotes

Question 3

Why is it advantageous that yeast has both haploid and diploid life cycle?

Answer 3

So studies can include both dominant and recessive genes

Question 4

How many years of evolution are yeast and human cells?

Answer 4

~600 million years

Question 5

What are the phases of the cell division cycle and how is it regulated?

Answer 5

G1, S, G2 and Mitosis
It is highly regulated

Question 6

What are the differences between the life cycle of S.cerevisiae and S.pombe?

Answer 6

S.cerevisiae buds after the G1 phase
S.pombe allows cells to bud off during G1

Question 7

What is used to regulate the life cycle of yeast?

Answer 7

Cyclin-dependent kinase (CDK)

Question 8

Which CDK interacts with phase-specific cyclins in S.cerevisiae?

Answer 8

Cdc28

Question 9

How is substrate specificity provided during the cell cycle?

Answer 9

When cyclins bind to CDKs

Question 10

What is the difference between the regulation in yeast and mammalian cells?

Answer 10

Mammalian cells are more complex as it contains different CDKs and cyclins

Question 11

What are the different cell cycle checkpoints?

Answer 11

G0:
Cells exit the cell cycle
G1:
Start in yeast, restriction point in mammals, growth factor control in mammals, nutrients in yeast, cell size control
G2-M:
Ensures DNA replication complete, cell big enough, good environment
M:
Ensures correct spindle attachment, triggers chromatid separation

Question 12

How can cancer develop from the cell cycle?

Answer 12

From mutations at the checkpoint mechanisms

Question 13

Which checkpoint is more susceptible to mutation?

Answer 13

The G1 phase checkpoint as it causes the cell to continue dividing, causing cancer

Question 14

What are 2 examples of cancer linked genes found in S.cerevisiae?

Answer 14

DNA repair gene - MSH2
Mutations associated with hereditary non-polyposis colon cancer, S.cerevisiae contains a gene with high homology to MSH2
Cell cycle checkpoint gene - ATM
Mutations are associated with Ataxia telangiectasia, increased sensitivity to ionizing radiation more than 100x likely to develop cancer
S.cerevisiae 2 genes high homology to ATM: MEC1 & TEL1

Question 15

What are the functions of the genes MEC1 and TEL1 in S.cerevisiae?

Answer 15

They encode a protein kinase involved in cell cycle control in response to DNA damage

Question 16

What is the function of ATM in humans?

Answer 16

It encodes a protein involved in a cell cycle checkpoint

Question 17

What is the function of the MSH2 gene?

Answer 17

It is involved in DNA repair

Question 18

How can yeast be used as a model to identify anti-cancer targets?

Answer 18

As synthetic lethal screens can be used for lethal pairwise combinations of gene mutations

Question 19

How can yeast be used to identify cancer?

Answer 19

It can be used to compare the cancerous cells to the normal cells

Question 20

How many genes does S.pombe contain?

Answer 20

~500

Question 21

What percentage of genes included “disease-associated” descriptions?

Answer 21

~6-7%

Question 22

What are examples of human disease genes found in S.cerevisiae?

Answer 22

WRN/BLM genes
Mutations are associated with Werner and Blooms syndrome, premature age-related defects in patients
High homology to WRN/BLM names SGS1
NF1
Mutations are associated with neurofibromatosis type 1 , single-gene disorder characterised by high incidence of complex cognitive symptoms
IRA1 & IRA2 encode proteins with similar biochemical activities in yeast

Question 23

What is the use of the SGS1 gene found in S.cerevisiae?

Answer 23

It is a helicase involved in genome stability