Cell Cycle Flashcards
Function of the Cell Cycle (4)
- reproduce and pass genetic info
- DNA is replicated
- DNA distributed to 2 identical daughter cells
- growth with division
Phases of Cell Cycle
- G1 (Gap 1) – generalized growth
- S (Synthesis) – DNA replication
- G2 (Gap 2) – preparation for segregation
- M (Mitotic) – segregation of chromatids
Mitosis Phases
Prophase Metaphase Anaphase Telophase Cytokinesis
Prophase
- nuclear envelope breaks down
- chromosomes condense
Metaphase
- chromosomes align at metaphase plate
Anaphase
- sister chromatids pulled towards spindle poles
Telophase
- chromosomes de-condense
- reformation of nuclei
Budding Yeast - S. cerevisiae
- cell cycle stage by size of bud
- long G1 phase
Fission Yeast - S. pombe
- elongation of ends
- formation of septum
- long G2 and M phase
G2 - M Transition in S. pombe
- loss of Cdc2 activity = can’t enter M phase
Cdc2
- cyclin dependent kinase
- activity regulated by amount of cyclin present
Protein Families Regulate Cell Cycle
- kinases
- phosphates
- cyclin
Mitosis Promoting Factor (MPF)
- heterodimer of CDK + mitotic cyclin
- formed at late G2
Cyclin Regulation
- cyclins activates CDKs
- 4 classes of cyclin (G1, G1/S, S, M)
- cyclin regulated at transcription + ubiquitin
Polyubiquination
- addition of Ub to a protein signals for protein to be degraded by proteasome
- cyclins targeted for destruction ubiquitination (controlled by SCF ubiquitin ligases)
Regulate MPF Activity
- addition or removal of phosphate group on CDK
- prevent premature activation
- Wee1 (inactive)
- Cdc25 and CAK (active)
Wee1
- kinase to phosphorylates CDK = INACTIVE
- remains in G2
- prevent premature activation
- CDK inhibitory kinase
Cdc25
- phosphatase to remove phosphate group from CDK = ACTIVE
- exit G2
- activating phosphatase
CAK
- kinase to phosphorylate CDK = ACTIVE
Active MPF Uses
Phosphorylation
- chromosome condensation
- disassemble nuclear envelope
- interphase microtubule disassembly
- block vesicular traffic
Exit Mitosis
- MPF inactivate at Anaphase
- cyclin degraded by polyubiquitination
- using Anaphase-Promoting Complex/Cyclosome (APC/C)
- recognizes destruction box in cyclin
Mitotic Cyclin Levels in Cell Cycle
- Metaphase = high activity
- Anaphase = APC/C + polyubiquitination (degraded in proteasome)
- Telophase = low activity
S Phase Entry
- phosphorylation of S-phase inhibitor (by G1/S cyclin)
- prevents premature initiation
- SCF ubiquitin ligase degrades inhibitor
- activates S cyclin
Cell Cycle Process (6)
1) G1/S CDKs activate + phosphorylate S-phase inhibitor
2) SCF ubiquitin ligase degrades inhibitor –> S-phase CDKs
3) SCF ubiquitin ligase degrades S cyclins
4) Cdc25 + CAK activate CDK –> CDK + M cyclin = MPF
5) Metaphase + Anaphase
6) APC/C degrades M cyclin