The Cell Cycle & Regulation Flashcards
Cell Cycle Phases (explain each)
Interphase
- G0 - dormant state, non cycling - G1 - between end of division and DNA replication for growth - S - DNA synthesis - G2 - between DNA replication and division
Division (M) - mitosis
Cell Division (M phase)
prophase, prometaphase, metaphase, anaphase, telophase
prophase
pt 1 of m phase
mitotic spindle forms
pro metaphase
pt 2 of m phase
nuclear envelope is gone, microtubules attach to chromosomes
metaphase
pt 3 of m phase
chromosomes aligned on mitotic spindle and attach
anaphase
pt 4 of m phase
sister chromatids pulled apart by m. spindle
telophase
final part of m phase
nuclear membrane reforms around new sets of chromosomes
What is Progression, Transition and Checkpoint
Progression - moving through cell cycle phase
Transition - one phase to another
-Checkpoints - cell mechanisms that control order/timing of cell cycle phase transitions to make sure DNA is correct before reproduction
How can we detect cell cycle phases
- Cells labeled with DNA-binding fluorescent dye
- Passed through cytometer
- Flurescence proportional to DNA content
- On histogram, two peaks shows G1 and G2/M phases, when Dan is highest; S is in between
Cell cycle regulators
1) Cyclins
2) Cyclin Dependent Kinases (CDKs)
Cyclins
- Cell cycle regulatory proteins
- 12 types
- Present during G1, S and G2/M phases
Cyclin-Dependent Kinases (CDKs)
- Serine/Threonine kinanses
- Dependent on cyclin concentration for activation
Cyclin and CDK pairings
-CDK4/CDK6 —— Cyclin D
-CDK2 ——— Cyclin E & Cyclin A
CDK1 ———– Cyclin A & B
How do cyclins activate CDKs and act on a substrate
1) Cyclin binds to CDK
2) CDK-activating kinase (CAK) phosphorylates CDK’s threonine residue (PSTAIRE a-helix) while Cdc25 dephsphorylates inhibitory phosphates.
3) Cyclin-CDK complex phosphorylates substrate proteins, changing activation status.
4) Change in reg protein dictates whether next phase begins
CDK4/CDK6 & Cyclin D Function and Dominant Activity
- Moves phase past restriction point at G1/S boundary
- Active during G1
CDK2 and Cyclin A/E Function and Dominant Activity
- Initiates DNA synthesis is S phase
- Cyclin A: active during S1
- Cyclin E: active during G1/S transition
CDK1 & Cyclin A/B Function and Dominant Activity
- Transition from G2 to M
- Cyclin A: active during S
- Clyclin B: active during G2
What does ubiquitin do
Targets cyclin for destruction via proteasome
What is responsible for Cyclin-CDK binding?
PSTAIRE alpha-Helix
What is Cdc25
A protein phosphatase that activates Cyclin-CDK complex and remove inhibitory phosphates
What is the order of cell phases?
G1, S, G2, M
What are CKIs and the relevant types?
Cyclin-dependent kinase inhibitor
- INK4: p16^Ink4a
- CKI: p27^Kip1
- CKI: p21Cip1/Waf1
CKI: p21 —- Cdk substrates and functions
- Most cdk-cyclin complexes
- Function:
1) Induced by p53 tumor suppressor
2) Stops cycle after DNA damage
3) Cycle stop at senescence
CKI: p57 —– Cdk substrates and Functions
- Most Cdk complexes
- Function:
- growth suppressors will make it stop the cycle