L18 Flashcards
what needs to happen to carry out a cell cycle
Chromosomes need to be duplicated
Other organelles need to copied
Cells need to grow
Chromosomes need to be segregated accurately
Cell needs to physically divide
what are the cell cycle steps
G1: Gap 1
S: Synthesis
G2: Gap 2
M: Mitosis
G0: resting state
which steps are the interphase
G1
S
G2
what happens in G1
In the cell cycle
- Deciding if conditions are right for a full cell cycle
- Growing and preparing for DNA synthesis
what happens in S phase
Replicating DNA and centrosomes
what happens in G2
Deciding if conditions are right for mitosis
what happens in mitosis
Chromosome segregation and cytokinesis
what happens in G0
Cells not in the cell cycle
- Terminally differentiated cells
- Quiescent cells (might divide)
- Senescent cells (never divide)
What drives the cell cycle?
Cyclin-dependent kinases (Cdks)
what are the features of Cyclin-dependent kinases (Cdks)
Protein kinases that transfer a phosphate onto their substrates
Act as “master regulators”
Have multiple target proteins to control numerous processes in the cell cycle
Cdks have little activity by themselves,
but they are activated by Cyclin proteins
Cyclins also influence the substrate specificity of Cdks
when are Cdks fully active
when cyclin, phosphatase, and Cdk-activating kinase (CAK) bind the Cdk
give an example of Cdk inhibitors CKIs
p27
How can we study cell cycle in mutant cells?
Temperature sensitive (ts) mutants
Mutations that allow gene products to function at low temperature, but not higher temperature
Track cell cycle by size and budding
What makes Cyclin levels oscillate?
Cyclin synthesis
Control of Cyclin destruction
how is cyclin synthesis maintained
changes in transcription and translation rate, which vary depending on cell type
give an example for the Control of Cyclin destruction
degradation of M-Cyclin is triggered by the APC/C
how does APC/C signal degrade M-Cyclin
The APC/C is a ubiquitin ligase
It covalently attaches the small protein Ubiquitin to client proteins such as M-Cyclin
what are checkpoints
Checkpoints are monitoring systems that check if conditions are right before allowing the next phase to occur
how do checkpoints work
Checkpoints act by promoting Cdk activation or inactivation
what do mitogens do
promote G1/S-cyclin synthesis (the start of the cell cycle)
what does DNA damage do to cyclins
inhibits cyclin activity by phosphoregulation or CKI
what prevents M-cyclin destruction
unattached chromosomes
where are checkpoints located
G1-S
G2-M
Metaphase-Anaphase
what happens in G1-S transition (START, Restriction Point, or G1 checkpoint)
The checkpoint asks:
Are nutritional conditions suitable? (particularly in single cell organisms)
Is the cell receiving proliferation signals? (particularly in multicellular organisms)
Has any DNA damage been repaired?
Was the previous mitosis too long?
Once passed, the cell is committed to the entire cell cycle
what happens in G2-M transition (G2 checkpoint)
The checkpoint asks:
Is DNA replication complete?
Has any DNA damage been repaired?
Is the cell big enough (yeast)?
what is Rad9 mutant yeast
mutant yeast that do not delay in G2 after DNA damage and they continue to proliferate with damaged DNA and eventually die
Rad9 is part of a checkpoint response, not part of the DNA repair response
true
what happens in Metaphase-Anaphase transition (Mitotic or Spindle Assembly Checkpoint, SAC)
The checkpoint asks:
Are chromosomes (properly) attached to the spindle?
Once the checkpoint is satisfied:
The APC/C is activated to degrade M-Cyclin
The cells exit metaphase into anaphase
when can cell cycle damage not be corrected
- extensive DNA damage
- trial and error correction of chromosome attachments takes too long
what happens to the cell cycle when damage cannot be fixed
Either:
Cells can withdraw from the cell cycle (senescence)
- Terminal exit from cell cycle
- Allows cell to remain part of tissue but it will not proliferate
Or:
Cells can undergo programmed cell death (apoptosis)
- Removes cell from organism
how do Checkpoints that don’t operate properly result in disease
- Aberrant mitogen signalling can inappropriately drive cells through the G1 checkpoint into the cell cycle
e.g. Cancer cells overexpressing EGF Receptors (EGFR, HER2), or with mutations in their signalling pathways (eg Ras mutants)
- Defects in the G2 checkpoint can allow proliferating cells to accumulate DNA damage
e.g. p53 mutations
- Defects in the mitotic checkpoint can cause aneuploidy (wrong number of chromosomes)
e.g. BubR1 mutation causing cancer predisposition syndrome (MVA)
