Cell Cycle (final) Flashcards
(58 cards)
What are the main phases of the cell cycle? What important events occur during each?
Prophase:
- Chromosomes condense
- Mitotic spindle assembles
Prometaphase:
- Nuclear envelope breaks down (triggered by phosphorylation and disassembly of NPCs and nuclear lamina) - catalyzed by M-Cdk
- Spindle MTs attach to kinetochores (links chromosomes to centrosomes)
Metaphase:
- Chromosomes align at equator of spindle (forms metaphase plate)
Anaphase:
- Cohesin linkages are degraded
- Sister chromatids separate and are pulled toward spindle poles
Telophase:
- Nuclear envelope reassembles around segregated chromosomes
- Mitotic spindle disassembles
- Chromosomes become decondensed
What are cyclins? How are they regulated?
(1)
* Concentration rises and falls at specific times during cell cycle
* Bind to Cdks
(2) Down side (degraded); up side: synthesized (de novo)
Describe three distinct ways Cdk activity can be regulated?
- Cyclin degradation
- Phosphorylation:
* Wee1 - inhibitory kinase; adds two inhibitory phosphates
- Cdc25 (cell division cycle 25) - activating phosphatase; plucks off inhibitory phosphates
- Inhibitory proteins
Compare and contrast the role of p21 and p27 in controlling the cell cycle.
Both:
- Suppress G1/S-Cdk and S-Cdk
p21:
- Activated by p53
- Suppress G1/S-Cdk and S-Cdk after DNA damage
- Prevents G1/S-Cdk and S-Cdk from driving cell into S phase
p27:
- attachment prevents G1-Cdk from phosphorylating target proteins required for progress through G1 into S phase
- suppresses G1/S-Cdk and S-Cdk activities in G1
- binds to G1/S-Cdk and S-Cdk (prevents them from driving cell into S phase)
- helps cell withdraw from cell cycle
- monitors cell growth (proper cell size)
What are mitogens? How do they function?
- Promote production of cyclins that stimulate cell division
- Act by switching on cell signaling pathways that stimulate synthesis of cyclins
What type of proteins are Rb and p53? How are they similar/different?
(1) Tumor suppressor proteins
Rb protein:
* Hold transcriptional regulators in inactive state
- Activated (inhibited) by mitogens
- Mitogens activates G1-Cdk and G1/S-Cdk
- G1-Cdk and G1/S-Cdk
phosphorylate (inactivate) Rb protein - Rb protein releases transcription regulators (activate genes required for entry into S phase)
p53:
* When DNA is damaged
* Phosphorylated by ATM kinase
* Responds to DNA damage in G1
* Activates p21
* Induces apoptosis if DNA damage is too severe
What are two distinct ways the cell can exit the cell cycle? How are they different?
- G0 (absence of mitogen)
- Terminally differentiated (withdraw from cell cycle permanently)
What conditions are required for passing the G 1/S checkpoint? How are G1-Cdk and G1/S-Cdk
activated? Once activated, how do these Cdks promote the transition past the checkpoint? Hint:
what is the role of Rb?
(1)
(2) Buildup of G1-cyclins and G1/S-cyclins
(3) G1-Cdk and G1/S-Cdk phosphorylate (inhibit) Rb protein -> release of transcriptional regulators that turn on genes required for entry into S phase
What are three things cells must do in order to divide?
- Duplicate their content (chromosomes, organelles, macromolecules, membrane)
- Partition duplicated contents, grows and split into daughter cells
- cells must grow twice the size (prevents tiny cells) - Coordinate all steps and machinery required for previous two processes
What is the duration of the cell cycle for the following cell types: (1) early fly embryo cells, (2) early frog embryo cells, (3) mammalian intestinal epithelial cells, (4) mammalian fibroblasts in culture
(1) 8 minutes
(2) 30 minutes
(3) ~12 hours
(4) ~20 hours
What is interphase? What are the three phases in interphase? What happens in each?
(1) Period between M phases
(2)
1. G1 phase - cell growth; gene transcription (gap phase between M phase and S phase)
- S phase - DNA replicates
- G2 phase - cell growth (gap between S phase and M phase)
Gene transcription occurs during G1 phase. Why not during mitosis?
Mitosis: chromosomes are highly condensed
What are the different types of cyclins?
M-cyclin - acts in G2 to trigger entry into M phase
G1/S-cyclin - activate Cdks in late G1; help trigger progression through Start; helps launch S phase
S-cyclin - helps launch S phase
G1-cyclin - act in G1; helps drive cell through G1 toward S phase
What is the anaphase-promoting complex (APC/C)?
- Ubiquitin ligase
- Complex that tags cyclins with ubiquitin
What causes Cdk to return to an inactive state?
Ubiquitylation of cyclin (marks protein for degradation in proteasomes)
Flies: nuclear syncytium
Frogs:
The eukaryotic cell cycle usually includes four phases. Why “usually”?
In some organisms early embryonic divisions lack G1 and G2
- Speeds up process
- Consequence: cells shrink by half during each division
What major events occur during interphase?
- Cell transcribe genes
- Cell synthesizes proteins
- Cell grows
What are the three major checkpoints? What is being checked in each?
- G1/S checkpoint:
- Is environment favorable? (growth factors, nutrients, correct size, DNA damage)
- Irreversible; typically involves external signaling
- Depends on proper signaling
- G2/M checkpoint:
- Is all DNA replicated? - Are all chromosomes properly attached to mitotic spindle?
What must happen if DNA replication is not completed? What about DNA damage? What happens if chromosomes are not aligned properly during mitosis?
Halt cell cycle
Describe Cdks.
- Do not work unless there is cyclin
- Must bind cyclin before it can become enzymatically active
- Always at high level in cell but not always on (only on when bound to cyclin)
How do Cdks control the timing of DNA replication (G 1➞S) and mitosis (G2➞M)?
Through phosphorylation and dephosphorylation of important target molecules
Cell-cycle control system overview
G1 –to– S transition: Cdk inhibitors keep cells from
entering S phase and replicating DNA
G2-to-M transition: activation of M-Cdk is suppressed by inhibiting the phosphatase (Cdc25) required to activate the Cdk
Exit from mitosis can be delayed by inhibiting activation of APC/C (preventing degradation of M cyclin)
What triggers breakdown of nuclear lamina?
M-Cdk
