The Cell Cycle and Cancer Flashcards
What happens in G1 checkpoint?
Makes sure there is enough energy and senses external cues, e.g. needing space
What happens in G2 checkpoint?
Mainly detects DNA damage and sees if the cell can repair them
What happens in M checkpoint?
Allows chromosomal segregation to occur correctly
Determines if the chromosomes are attached correctly to the microtubule
When are CDKs active?
When cyclins are bound
What do CDKs do?
Phosphorylate a number of proteins which drive the cell cycle
Why are CDKs inactive normally?
Their active sites are blocked so their is no substrate or ATP binding
What is the role of cyclins?
To activate CDKs
They provide substrate specificity
What do mitogens do?
Activate TFs, e.g. Myc and Fos, to induce cyclin D
What does E2F do?
Induce cyclin E and A
What does FoxM1 do?
Induces cyclin B
What does cyclin D activate?
E2F
What does cyclin A activate?
FoxM1
What ubiquitin ligases degrade cyclin E?
SCF ligase (Skp, Cullin and F-box)
What ubiquitin ligase degrades cyclin A and B?
Anaphase promoting complex/ Cyclosome (APC/C)
What is the advantage of sing protein degradation in the cell cycle?
Unidirectional movement
Describe the positive feedback mechanism of cyclinB:CDK1
CyclinB:CDK1 is inhibited by Wee1/My1 which causes CDK1 phosphorylation
When cyclinB:CDK1 is in the active conformation, it inhibits Wee1/My1 and activates CDC25 phosphatase to dephosphorylate CyclinB:CDK1 so more is in the active conformation
Describe the positive feedback mechanism of cyclinE:CDK2
Mitogens induce the binding of p27 (inhibitor) to cyclinE:CDK2
When cyclinE:CDK2 is in the positive conformation, it phosphorylates and inhibits p27
What inhibits the phosphorylation of p27 by CyclinE:CDK2?
SCF ligase
When is E2F in an inactive form?
When it is bound to Rb
What inhibits the binding of Rb to E2F?
Phosphorylation by CyclinD:CDK4/6
What stimulates CyclinD:CDK4/6?
Growth conditions
What percentage of tumours are aneuploid?
80-90%
What is chromosomal instability caused by?
Frequent errors in mitosis
What is chromosomal instability associated with?
Poor patient prognosis
Metastasis
Resistance to chemotherapies
What phenotype is worse, having too many or too little chromosomes?
Having too many
What happens during the mitotic checkpoint?
Unattached kinetochores produce mitotic checkpoint complex (MCC) -> Inhibits the anaphase promoting complex (APC) -> when all kinetochores are attached then MCC production stops -> APC becomes active and degrades Cyclin B and Securin -> Mitosis
How do microtubules bind to kinetochores?
Randomly
Negatively charged microtubules bind to positively charged kinetochores
What is securin?
An inhibitor of separase
What is separase function?
It cleaves the bond which holds sister chromatids together
What is the process of error correction?
Aurora B removes kinetochore-microtubule attachments -> Correct attachments pull away from aurora B -> These are then insensitive to aurora B -> Allows specific correction of attachment errors
In terms of the cell cycle, why are tumour suppressors important?
Without tumour suppressors, the cyclins are not degraded and cell cyclin will continue when it is not meant to
What CDK binds to cyclin E?
CDK2
What CDK binds to Cyclin D?
CDK4/6
What CDK does Cyclin B bind to?
CDK1
