L20: Yeast as a Human Disease Model Flashcards
Why is yeast a good model for human genetic disease?
The diseases are commonly associated with conserved fundamental processes such as the cell division cycle
What are the advantages of using S.cerevisiae and S.pombe?
-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
Why is it advantageous that yeast has both haploid and diploid life cycle?
So studies can include both dominant and recessive genes
How many years of evolution are yeast and human cells?
~600 million years
What are the phases of the cell division cycle and how is it regulated?
G1, S, G2 and Mitosis
It is highly regulated
What are the differences between the life cycle of S.cerevisiae and S.pombe?
S.cerevisiae buds after the G1 phase
S.pombe allows cells to bud off during G1
What is used to regulate the life cycle of yeast?
Cyclin-dependent kinase (CDK)
Which CDK interacts with phase-specific cyclins in S.cerevisiae?
Cdc28
How is substrate specificity provided during the cell cycle?
When cyclins bind to CDKs
What is the difference between the regulation in yeast and mammalian cells?
Mammalian cells are more complex as it contains different CDKs and cyclins
What are the different cell cycle checkpoints?
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
How can cancer develop from the cell cycle?
From mutations at the checkpoint mechanisms
Which checkpoint is more susceptible to mutation?
The G1 phase checkpoint as it causes the cell to continue dividing, causing cancer
What are 2 examples of cancer linked genes found in S.cerevisiae?
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
What are the functions of the genes MEC1 and TEL1 in S.cerevisiae?
They encode a protein kinase involved in cell cycle control in response to DNA damage
What is the function of ATM in humans?
It encodes a protein involved in a cell cycle checkpoint
What is the function of the MSH2 gene?
It is involved in DNA repair
How can yeast be used as a model to identify anti-cancer targets?
As synthetic lethal screens can be used for lethal pairwise combinations of gene mutations
How can yeast be used to identify cancer?
It can be used to compare the cancerous cells to the normal cells
How many genes does S.pombe contain?
~500
What percentage of genes included “disease-associated” descriptions?
~6-7%
What are examples of human disease genes found in S.cerevisiae?
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
What is the use of the SGS1 gene found in S.cerevisiae?
It is a helicase involved in genome stability
