Cell Cycle Flashcards
Describe G1 phase.
Metabolically active
Largest segment of the cell cycle
Exception: early cell divisions of embryos proceed without growth phase
Describe G2 phase.
Preparation for mitosis - makes required enzymes and proteins
4 hours
What is minichromosome maintenance helicase? (MCM)
Enzyme that binds to replication origins which prepares the ORC for initiating replication
How is the re-initiation of replication prevented?
Kinase activity during late G1/S
What is the restriction point?
The point the cell is committed to dividing.
Located in late G1 phase
What is Mitotsis or Maturation Promoting Factor?
CDK1 and Cyclin B
What is CDK Activating Kinase (CAK)?
Phosphorylates CDK1 and activates it when its bound to Cyclin B
What is Wee1 kinase?
Adds an inhibitory phosphate to CDK1 and allows CB/CDK1 complex to increase in the cell
What Cyclin/Cdks are active during early G1 through R?
Cdk4,6
Cyclin D
What Cyclin/Cdks are active during the G1 to S transition?
Cdk2
Cyclin E
What Cyclin/Cdks are active during G2 to M transition
Cdk1
Cyclin B
What are four mechanisms of Cdk regulation?
Association of Cdks with cyclins - cyclin synthesis and degredation
Phosphorylation of Cdk - CAK and Wee1
Dephosphorylation - Cdc25 phosphatase
Association with Cdk inhibitors
What are the Ink 4 family of Cdk inhibitors?
Inhibitors that binds Cdk4,6 and inhibits progression through G1
What are the Cip/Kip family of Cdk inhibitors?
p21, p27, p57
Binds Cdk2/Cyclin A or E and inhibits progress through G1 and S
What external signal initiates the cell cycle?
Growth factor binding initiates a signaling cascade leading to synthesis of Cyclin D.
If growth factor signaling continues until the cell passes R, then the cell cycle will be completed
What is Retinoblastoma protein? (Rb)
Key regulator of transcription of genes required for cell cycle progression and DNA synthesis
What is the mechanism of Rb protein?
Not phosphorylated - binds E2F and represses transcription
Phosphorylation by Cdk4,6/CD - dissociates from E2F and transcription is active
How does the cell pass the R point?
Prior to R, Cdk2/Cyclin E is inhibited by p27
As G1 progresses, more CE is made and p27 is releived
p27 synthesis decreases, p27 binds Cdk4,5/CD, p27 is degraded
What are checkpoints?
Points in each phase that coordinate events to ensure that the next phase does not begin before that phase is completed
What are the two types of checkpoints?
DNA Damage checkpoints - protect cell from replication errors
Spindle Assembly Checkpoint - ensures chromosomes are aligned properly
Where are the DNA damage checkpoints?
G1, S, G2
Where is the Spindle Assembly checkpoint?
M phase - monitors alignment of chromosomes on the metaphase plate
What are ATM and ATR?
Kinases that are part of damage recognition complexes
Phosphorylate downstream kinases Chk1 and Chk2 when activated by DNA damage
What is the role of Chk1 and Chk2?
phosphorylate Cdc25, preventing activation of Cdk1 and Cdk2
What is p53?
A transcription factor that regulates the transcription of p21
Phosphorylated by ATM and Chk2
Increases levels of p21 which inhibits Cdk2/CE
Frequently mutated in cancers
