3.1 Cell Cycle Flashcards
What is the 4 phases of the cell cycle?
G1, S, G2, M
What happens in S phase?
DNA synthesis
What happens in M phase?
Separate chromosomes and divide cells
What are GAP phases used for?
Allows more time for growth
What are the 3 checkpoints in the cell cycle?
Checkpoint I Start, Checkpoint II G2/M, Checkpoint III metaphase to anaphase
What are the 3 checkpoints in the cell cycle?
Checkpoint I Start, Checkpoint II G2/M, Checkpoint III metaphase to anaphase
What does Checkpoint I Start do?
Cell commits to cell cycle entry and chromosome duplication
What does checkpoint II G2/M do?
Chromosome alignment on spindle in metaphase
What does checkpoint III do?
Trigger sister chromatid separation and cytokinesis
The cell cycle control system uses a series of biochemical switches made of what?
Cdks
What do Cdks turn on and do?
Turn on various steps of the cell cycle and P proteins downstream to activate them and regulate cell cycle events
What is the heart of the cell-cycle control system?
Cdks
True or False? Cdks levels remain constant during cell cycle
False. Rise and fall
The cell cycle is governed by what?
Cdks
True or False? Cdks activities remain constant during cell cycle
False. Rise and fall
What proteins regulate cdks?
cyclins
Cdks are dependent on what?
cyclins
Cdks must be bound to cyclin to have what type of activity?
protein kinase
True or False? Without cyclin, cdk inactive
True
cyclin expression in cells controls what?
what step cell is in the cell cycle
What directs cdks to their specific target?
cyclins
What directs cdks to their specific target?
cyclins
what are the 4 classes of cyclins?
G1/S, S, M and G1
What 4 things do the G1/S cyclins do?
Activate Cdks in late G1. Help trigger progression through START. Commitment made to cell cycle entry. Levels drop in S phase
What 4 things do S cyclins do?
duplicate DNA, bind Cdks after progression through START, help stimulate chromosome duplication, S-cyclin levels remain high until mitosis
What do the M-Cyclins do?
Activate cdks that stimulate entry into mitosis at G2/M checkpoint. M-cyclins removed at mid-mitosis
What do G1 cyclins do?
Govern activity of G1/S cyclins
What of cdks rise and fall during the cell cycle?
Activities
What of cyclins rise and fall during the cell cycle?
Levels
What of cyclins rise and fall during the cell cycle?
Levels
Without cyclin bound, the active site of cdk is blocke by a region of the protein called what?
T loop
What causes the T-loop to move out of the active site?
Binding of cyclin to cdk
P of Cdk at t-loop does what to the enzyme?
Fully activates it
What P cdk?
CAK
What two proteins inhibit Cdk activity?
Wee1 kinase and CKI
How does Wee1 kinase inhibit Cdk activity?
By P the roof site
What enzyme reverses Wee1 kinases P of the roof site?
Cdc25
How does CKI inhibit cdk activity?
CKI binds to both cdk and cyclin to inactivate it
What is the primary purpose for CKI to inhibit cdk activity?
To control G1/S cdks + S cdks early in cell cycle.
What is p53?
tumor suppressor
What does p53 influence?
expression of many genes
p53 up regulates what?
p21
what is p21?
a CKI to stop cell division
What is a target of p53?
p21 transcription
how does cancer happen pertaining to p53 and p21?
If p53 fails there will be lower p21 expression and without this CKI cells divide uncontrollably.
What is another control of cyclin-cdk activity at S phase?
Proteolysis
S cyclin cdk complex is important to start what?
DNA replication
How are s-cyclin cdk complexes inhibited by?
Binding to CKI
How does s cyclin cdk complexes release CKI?
proteolysis
How does CKI get removed from s-cyclin cdk?
By an enzyme called SCF-ubiquitin ligase that adds ubiquitin to CKIs
SCF activity depends on what?
F-Box subunit
What part of the cell cycle does SCF add ubiquitin to CKI?
G1
What controls mitosis?
M cyclin-cdk
Why is M-cdk usually in the inactive form?
Wee1 holds M-cdk in inactive state
What phase of the cell cycle has lots of primed inactive M-cdk around?
G2
What activated M-cdk?
Cdc25
What type of feedback is m-cdk activation?
positive
What is mitosis?
Progression from metaphase to anaphase
How is mitosis triggered?
By protein destruction
What is a key regulator for mitosis?
APC/C
What family is APC/C part of?
ubiquitin ligase
What does APC/C do?
addition of ubiquitin to proteins to cause destruction
What two major proteins are affected by APC/C?
Cohesion and securin
What does cohesin do?
glues together sister chromatids
What does securin do?
protects cohesin proteins linkages
What does separase do?
undoes glue holding chromatids together
how does securin protect cohesins?
inhibits separase.
What is the order of APC/C and mitosis?
APC/C levels rise in mid mitosis, APC/C adds ubiquitin on targets, APC/C destroys cyclins and complexes, destruction of securin, separase active thus cleaves cohesin, sister chromatids come apart.
What enzymes are a major target for APC/C?
S and M cyclins
How is APC/C activated?
by binding to Cdc20
When moving to anaphase APC/C wants to get ride of what two enzymes?
S and M cyclin
What are the first 4 steps of the cell cycle control system?
- Activation of G1-cdk. 2. G1 cdk stimulated genes making G1/S-cyclin + S-cyclin. 3. Go through START checkpoint. 4. G1 S cdk activity induces S cdk activity causing DNA replication
What are the final 3 steps of the cell cycle control system?
- M cdk drives expression through G2/M checkpoint. 6. APC/C + Cdc20 triggers destruction of securin and cyclins at metaphase to anaphase transition. 7.Completion of mitosis.
Mitosis cell cycle regulation occurs in 2 parts, what are they?
- Increase of M cdk activity at G2/M triggers prophase, prometaphase and metaphase. 2. Metaphase-to anaphase transition
What happens during the first part of the cell cycle regulation
assembly of mitotic spindle, and attachement to sister chromatids
what happens during the 2nd part of the cell cycle regulation?
APC/C destroys securin, which securin can no longer inhibit separase thus cleaves cohesin. APC/C triggers destruction of cyclins that leads to cdk inactivation and de P of cdk targets
For DNA replication what 2 problems must the cell solve?
Replication of DNA with complete accuracy and every nucleotide is copiesd once to prevent amplification
Describe the 3 checkpoints in the cell cycle*
Checkpoint I Start: Cell commits to cell cycle entry and chromosome duplication, Checkpoint II G2/M: Chromosome alignment on spindle in metaphase, Checkpoint III metaphase to anaphase: Trigger sister chromatid separation and cytokinesis
Name 2 ways of regulating cyclin cdk complexes*
inhibitory proteins:Wee1 kinase and CKI and APC/C
Describe the order of events involving APC/C cdc20, securin, separase and cohesin in sister chromatid separation.
APC/C levels rise in mid mitosis by activation of Cdc20, APC/C adds ubiquitin on targets, APC/C destroys cyclins and complexes, destruction of securin, separase active thus cleaves cohesin, sister chromatids come apart.