31st Jan Flashcards
What is hyperplasia?
The loss of control of cell growth
What is dysplasia?
The change of cell properties due to accumulation of genetic damage
How long is the average human cell cycle?
24 hours
What are the stages of mitosis?
Prophase Pro-metaphase Metaphase Anaphase Telophase
What conformational changes occur in Cdk upon cyclin binding?
PSTAIRE andthe activation loop shift
What Cdk-cyclin complexes are required for the passage through the restriction point?
Cdk4 and Cyclin D
Cdk6 and Cyclin D
What Cdk-cyclin complex is required for entry into S phase?
Cdk2 - Cyclin E
What Cdk-cyclin complex is required for passage through S phase?
Cdk2-cyclin A
What Cdk-cyclin complexes are required for entry into mitosis?
Cdk1-cyclinA
Cdk1-cyclinB
Who identifies Cdks in yeast?
Lee hartwell and Sir Paul Nurse
Outline the network in yeast for G2–>M transition
Wee1+ inhibits Cdc2
Cdc25 stimulates Cdc2
Cdc2 and Cdc 13 stimulate G2–>M
How is Cdk regulated by phosphorylation?
Inactive cdk-cyclin is phosphorylated by 2 opposing kinases. This means it is inhibited.
One kinase is removed by a phosphatase –> activation
How does cdk-cyclin B’s localisation change through the cell cycle?
During interphase it is mainly present in the cytoplasm
During mitosis it is in the nucleus and surrounding mitotic spindles
Who discovered cyclins?
Tim Hunt
What are CKIs?
Cdk inhibitor proteins
What are the 2 families of CKIs?
p16
p21/p27
What is the role of p16?
Binds Cdk4/6 preventing cyclin binding
What is the role of p21/p27?
inds Cdk2 inactivating it however still allowing the cyclin to bind
How do growth factors regulate the levels of cyclin D?
They stimulate it and growth inhibitors inhibit it
How do growth factors regulate the levels of CKIs?
they inhibit them and growth inhibitors stimulate them
What are cell cycle checkpoints?
Points at which the response of the cell to both intracellular and extracellular signals, in reference to the cell cycle is decided
Which checkpoints are commonly lost in cancer?
Restriction Point
DNA damage
DNA replication stress
Mitotic spindle assembly
What are the cancer treatment methods which target the cell cycle checkpoints?
Microtubule inhibitors e.g. Vinca alkaloids
Anti-metabolites e.g. Methotrexate
DNA Binding Agents eg. Alkylating agents
How do chemotherapeutics targeting cell cycle checkpoints cause severe side effects?
Killing gut epithelia –> nausea, vomiting and diarrhoea
Killing immune cells –> Immune suppression
Killing erythrocyte precursors –> anaemia
Killing hair follicle cells –> hair loss
