Brazeau - Cell Cycle Flashcards
Aneuploidy
Abnormal number of chromosomes Can cause over or under production of genes
Four phases of cell cycle
G1 S G2 M Interphase between M phases
Growth Phases? Replication of the DNA? Segregation of the DNA
G1 / G2 S Phase M Phase
What is the largest segment of the cell cycle?
G1 Phase
What is the exception to the G1 phase?
Early cell divisions of embryos proceed w/out G1/G2 phase
G2 Phase
Second growth phase, preparation for mitosis
What is main regulator of DNA replication? What prevents re-initiation of replication?
MCM helicase kinase activity during late G1/S
What controls entry into the cell cycle?
Availability of growth factors
What links cell division to conditions in the cell’s environment?
Growth factors
These will initiate cell division
Signaling Cascades
Downstream mediators of growth factors
Cyclins
Regulate activity of cyclin dependent kinases
Cyclin Dependent Kinases (CdK)
Activate components of pathways responsible for DNA synthesis and events of mitosis
Cdk Inhibitors
Provide additional control in specific situations
e.g Absence of growth signals or DNA damage
Checkpoints
Additional regulation, “quality assurance”
What compound regulates the transition from G2 to M?
MPF (CycB / Cdk 1)
What binds to cyclins dependent kinases to regulate their activity?
Cyclins
MPF
Mitosis Promoting Factor
Cyclin B / CDK 1
Regulates G2 - M
What occurs following Cyclin B binding to Cdk1 (forming MPF complex)?
- CDK Activating Kinase (CAK) Adds +P to CDK1
- Wee1 Kinase Adds Inhibitory +P to CDK1
- Cdc25 removes inhibitory-P
- Active MPF initiates M phase
- APC ubiquitinates and targets for proteosomes
CAK
Activating kinase, phosphorylates Cdk1 for activation
Wee1 Kinase
Adds inhibitory phosphate to Cdk1
Cdc25 Phosphatase
Removes inhibitory phosphate added by Wee1 Kinase
What tags Cyclin B for degradation?
APC ubiquitinates
CdK/Cyclin: Early G1 - R
Cdk 4,6/CycD
CdK/Cyclin: G1 - S
Cdk2/CycE
CdK/Cyclin: G2 - M
Cdk1/CycB
What major complexes regulate Cdks?
Cyclin
CAK (activate)
Wee1 (inhibit)
Cdc25 (activate)
CKI (inhibit)
Ink 4 Family
Cdk 4,6 Inhibitor
Inhibits progression through G1
Cip/Kip
Cdk2/CycE (or A) inhibitor
Blocks progress through G1 and S
Often involved in cancer
What does growth factor binding to its receptor trigger?
What happens if GF removed before R?
After?
Synthesis of Cyclin D (need to build this up)
Cell will enter G0
Cell cycle will be completed
Major growth factors for Cyc D synthesis?
Ras/Raf
MEK/ERK
What drives the cell cycle through the R-point in G1?
Cdk4,6/Cycd
What are main targets of Cdk4,6/CycD?
Retinoblastoma Protein (Rb)
When not phosphorylated, is the role of Rb?
When phosphorylated?
What kinase phosphorylates the complex?
Binds E2F, and represses transcription genes for cell cycle progression
Rb dissociates from E2F; transcription proceeds
Cdk4,6/CycD
What does passage through R and initiation of DNA synthesis require?
What inhibits this until the proper time?
How is this inhibition removed?
What occurs once this inhibition is removed?
Activation of Cdk2/CycE
KIP family (p27)
CycE synthesis increases, p27 decreases
DNA synthesis begins
DNA Damage Checkpoints
Protect cell from replication errors or pasisng down damaged DNA
Spindle Assembly Checkpoint
Ensure chromoosmes are aligned properly so each daughter cell receives one copy of each chromosome
How many DNA damage checkpoints are there?
How many spindle assembly checkpoints are there?
3x
G1
S
G2
1x
M
ATM/ATR
Kinases part of damage recognition complexes; phosphorylate downstreak kinases–
Chk1 / Chk2
Chk1/Chk2
Downstream kinases which phosphorylate Cdc25; blocking Cdk1 and Cdk2
What phosphorylates p53?
ATM/Chk2
p53
Transcription factor that regulates trasncription of CKI 21; increases lead to increas in p21.
p21 inhibits Cdk2/CycE complex, causing G1 arrest
