Lecture 12 Cell cycle and death Flashcards
the cell cycle
- cell growth and chromosome replication
- chromosome segregation
- cell division
interphase
M phase
interphase: G1, S, M
M phase: mitosis + cytokinesis
mitosis
prophase metaphase anaphase telophase
control systems of the cell cycle
3 major regulatory checkpoints:
Start = restriction point: in the late G1, cell commits to chromosome duplication
G 2/M point: system triggers chromosome alignment
metaphase-to-anaphase transition: system stimulates chromatide separation and pushes to the completion of the cycle and initiation of cytokinesis
the cyclins
- G1/S cyclins trigger progression through start point
- S cyclins trigger DNA replication
- M-cyclins trigger mitosis
- APC/C complex triggers anaphase
each cyclin activates specific cyclin-dependent protein …
kinases
The level of Cdks is constant (constitutive) in the cell, but the level of … change.
cyclins
The oscillation in levels of cyclins (synthesis and degradation) is the main mechanism for regulating the Cdks activity, but not the only one. Other important mechanisms are also involved:
- phosphorylation of the cyclin-Cdk complex by the kinase Wee1 inhibits its kinase activity
- dephosphorylation of the same residues by the phosphatase Cdc25 increases the activity
- binding of Cdk inhibitor proteins (e.g. p27) to the complex rearranges the active site of the kinase and renders it inactive
Onset of mitosis depends mainly on the protein kinase M-Cdk. When activated, M-Cdk activates the following processes:
- induction of assembly of mitotic spindle
- attachment of sister chromatides to the opposite poles of the spindle
- chromosome condensation
- breakdown of nuclear envelope
- rearrangement of actin cytoskeleton and Golgi apparatus
activation of M-Cdk
M-cyclin gradually accumulated in the cell
Cdk1 in complex with M-cyclin gets phosphorylated by CAK, catalyzed by Wee1
inactive complex building up
Phosphatase Cdc25 removes the inhibitory phosphate
-> M-Cdk complex active
+ two positive feedback loops
M -Cdk initiates the spindle assembly in …
Prophase
Spindle attaches to … on chromosomes
kinetochore
prophase
1
prometaphase
2
metaphase
3