Cell cycle Flashcards
What are the main phases of the cell cycle?
G1: Growth and preparation for DNA replication.
S: DNA synthesis (replication).
G2: Preparation for mitosis.
M: Mitosis (cell division).
Variations:
G0: Quiescent state (e.g., neurons).
Endocycle: S phase without mitosis (polyploid cells).
Endomitosis: Mitosis without cytokinesis (e.g., megakaryocytes
Cyclin-Dependent Kinases (CdKs)
To phosphorylate target proteins, regulating progression through the cell cycle. CdKs require cyclins for activity.
How do cyclins regulate CdKs?
Cyclins bind to CdKs, forming active complexes. Cyclin levels fluctuate, determining CdK activity at specific stages (e.g., G1/S-, S-, M-cyclins).
How does G1/S-CdK promote S-phase entry?
G1/S-cyclins accumulate and bind CdK.
Active G1/S-CdK phosphorylates Retinoblastoma (Rb), releasing E2F transcription factors.
E2F activates transcription of S-phase genes (e.g., S-cyclin, DHFR).
How does DNA damage block G1/S transition?
DNA damage activates ATM/ATR → Chk1/Chk2 → p53.
p53 induces p21, which inhibits G1/S-CdK and S-CdK, halting the cycle.
How is M-CdK activated?
M-cyclins accumulate in G2.
Wee1 phosphorylates/inhibits M-CdK.
Cdc25 phosphatase removes inhibitory phosphates, activating M-CdK.
Positive feedback loops:
M-CdK inactivates PP2A-B55 (via Greatwall kinase).
M-CdK inhibits Wee1 and activates Cdc25.
What happens if DNA damage is irreparable?
Multicellular organisms: p53 triggers apoptosis.
Single-cell organisms: Continue division despite damage.
What is the role of APC/C-Cdc20?
Ubiquitinates securin (activating separase to cleave cohesions) and S/M-cyclins (inactivating CdKs).
Regulated by Mad2 at the spindle checkpoint.
How does the spindle-attachment checkpoint work?
Unattached kinetochores activate Mad2, which binds APC/C-Cdc20, blocking anaphase until all chromosomes are attached.
What is the role of p53?
Transcription factor activated by DNA damage.
Induces p21 to inhibit CdKs, arresting the cell cycle.
How does PP2A-B55 regulate M-CdK?
Dephosphorylates Cdc25 and Wee1, suppressing M-CdK.
Inhibited by Greatwall kinase during mitosis.
Primary function of CdKs?
Phosphorylate proteins to regulate progression.
Cell most likely to enter G0?
Neurons.
What is APC/C’s role?
Marks securin and cyclins for degradation via ubiquitination, enabling anaphase and CdK inactivation.
Describe M-CdK’s positive feedback loops.
A:
M-CdK activates Cdc25 and inhibits Wee1 → more active M-CdK.
M-CdK inhibits PP2A-B55 (via Greatwall) → reduced dephosphorylation.
How is separase regulated?
Securin binds and inhibits separase.
APC/C-Cdc20 degrades securin in metaphase, freeing separase to cleave cohesins.
How do CKIs regulate the cell cycle?
Bind to CdK-cyclin complexes (e.g., p21/p27 inhibiting G1/S-CdK) to block activity.
