Week 11 - Cell Cycle Flashcards
What are the steps in the cell cycle
(G1->S->G2)*->M
*interphase
What are the stages of M phase
Prophase, prometaphase, metaphase, anaphase, telophase
What happens during G1
Cell is metabolically active and growing
What happens during S phase
DNA replication
What happens during G2
Cell growth continues and proteins synthesised in preparation for mitosis
What acts as a control point between G1 and S phase
START/restriction point
What happens when appropriate growth factors aren’t present in G1
The cell enters G0
What causes progression from G2 to S phase
Hormonal stimulation
Name when all 4 cell cycle checkpoints occur
Restriction point
DNA damage in S phase
DNA damage in G2
Spindle assembly during M
How is it ensured that the genome is only replicated once per cell cycle
MCM proteins are displaced from ORC so that replication cannot happen until after mitosis
Which 2 ways can we analyse the cell cycle
Flow cyclometer or fluorescence activated cell sorter
What three experiments contributed to identifying cell cycle regulatory molecules
Studies of frog oocytes
Genetic analysis of yeast
Protein synthesis in sea urchin embryos
What did the study of frog oocytes show
Maturation protein factor was responsible for entering a cell into M phase from G2
What did the analysis of yeast show us
cdc genes are needed to pass through START and entry into mitosis; they encode protein kinases
What is the human equivalent of cdc
Cdk1
What did the sea urchin experiment show
Cyclins accumulate in interphase and rapidly degrade at the end of mitosis
What was deduced when these experiments were merged
Cyclin A provides transition into M phase and MPF was a mix of Cdk1 and cyclin B
Without cyclin B being bound to Cdk1 proteins can’t be phosphorylated and cell cycle doesn’t progress
When is Cdk1 active and inactive
Active when it’s dephosphorylised and inactive when it becomes phosphorylised
What happens when cyclin B is degraded
Cell exits mitosis and undergoes cytokinesis and returns to interphase
What 4 mechanisms regulate activity of Cdks
Association to cyclin partners
Activation of complexes needs phosphorylation of threonine at position 160
Inhibitory phosphorylation catalysed by Wee1
Binding of cdk inhibitors
How are D type cyclins important
Provide one link between growth factor signalling and cell cycle progression
What pathway do growth factors stimulate cyclin D1 synthesis through
Ras/Raf/MEK/ERK pathway
What happens to the cell cycle and cyclin D1 if growth factors are present through G1
Cdk4,6/cyclin D1 complexes will drive cells through the restriction point
What can be caused by cyclin D1 regulatory defects
Cancer
What does Rb gene do
Is as a tumour suppressor gene by slowing down the progression of the cell cycle
How does Rb work
In G0 or early G1, Rb binds to E2F transcription factors to suppress gene expression involved in cell cycle progression
How is Rb dissociated
It is phosphorylated by cdk4,6/cyclin D as the cell passes the restriction point
What happens after Rb is phosphorylated
E2F stimulates cdk2/cyclin E which leads to activation of MCM helicase, initiating DNA replication
Which protein kinases mediate cell cycle arrest
ATM and ATR
When are ATM and ATR activated
When DNA is damaged
What does ATM recognise
Double strand breaks
What does ATR recognise
Single stranded or unreplicated DNA
What does ATM and ATK do after recognising defects
Phosphorylate Chk1 and Chk2
What do Chk1 and Chk2 do
Phosphorylate cdc25 to inhibit it and cause cell cycle arrest since cdk1 and cdk2 become inhibited
Cdk1 causes arrest in G2
Cdk2 causes arrest in G1 and S
