1
Q
Explain the importance of the cell cycle
A
- Controls proliferation / regulation of somatic cell number
- Ordered series of events leading to replication of cells
- Maintains homeostasis
- DNA undergoes replication, transcription and translation
- Rate of cell death = Rate of cell division
2
Q
Briefly describe the phases of the cell cycle
A
- Interphase: Period between cell divisions, growth, development and preparation, G1, S, G2
- M Phase: Mitosis, nuclear divison / cytokinesis, PMAT
3
Q
What occurs in G1 phase
A
- Gap phase between M and S
- Cell grows, undertakes normal metabolism and syntheses proteins in preparation for cell division, 9 hours
- Contains start checkpoint of cell division, passing this point commits cell to cell division
- Cells can exit prior to this checkpoint (G0 phase)
4
Q
What occurs in G0 phase
A
- During G1 cells may exit cycle in response to regulatory signals
- Enter a non-dividing (quiescent) state, resting phase
- May enter or not, able to re-enter G1
- Cells may stay here for an extended period or indefinitely, rapidly dividing cells don’t enter
5
Q
What occurs in S phase
A
- Synthesis phase
- DNA is replicated to make an identical copy of each chromosome (sister chromatids)
- Amount of DNA double 2n - 4n, nucleus enlarged, 10 hours
6
Q
What occurs in G2 phase
A
- Gap phase, further growth
- Prepare for mitosis, DNA / centrosome replicates, 4.5 hours
- Centrosome: Produces microtubules, microtubule organising centre (MTOC), contains two centrioles at right angles where microtubules assemble
7
Q
What occurs in M phase (mitosis)
A
- P: Nuclear membrane disintegrates, nucleolus disappears chromosomes condense, mitotic spindle forms, kinetochores mature & attach spindle
- M: Kinetochores attach chromosomes to mitotic spindle and align along metaphase plate (equidistant )
- A: Kinetochore microtubules shorten, separating sister chromatids to opposite poles (disjunction)
- T: Chromosomes reach poles, kinetochores disappear, nuclear membrane re-forms, nucleolus reappears, chromosomes de-condense
- C: Cleavage furrow forms at equator of cell & pinches inward until cell divides in two, formed by a system of actin filaments pinching in a contractile ring
8
Q
What are checkpoints in the cell cycle
A
- Ensure the next cell cycle event is not activated before the preceding one has been completed or before errors that occurred during the preceding step have been corrected, brakes on CC
- Progression of cell cycle is crucial to production of progeny cells with correct number of chromosomes
- Proliferation is controlled by checkpoints that prevent progression until preceding stage is successful
- Cellular environment is stable
9
Q
What are examples of checkpoints in the cell cycle
A
- R-Restriction Point: External checkpoint-late G1, where the CC becomes independent of mitogens, regulated by growth factors, environment, oxygen, unfavourable conditions
- S-Phase Internal Checkpoint: G2, monitors whether DNA replication is complete & if DNA damage has been repaired, mitosis will not proceed if cell ‘fails’
- Mitosis: Metaphase, checkpoint identifies whether chromosomes correctly attached to spindles & spindles formed properly, allows exit from m phase
10
Q
How does cell loss and proliferation balance occur
A
- Pathways are linked at various points, apoptosis may be induced in cells that fail successfully to complete a phase of the cell cycle
- Cells die and are replaced, cell loss is accidental / through programmed apoptosis
- Cell loss not a problem as long as cell population is replenished
11
Q
What is cyclin dependent protein kinase (CDK)
A
- Controls substrate specificity and phosphorylation activity
- Each CDK subunit can associate with various cyclins
- As different cyclins present at different stages of cell cycle, each phase is characterised by phosphorylation of different target proteins
- CDK promotes own activation and own inactivation
12
Q
Explain how cyclin levels oscillate with cycle phase
A
- CDK protein abundance remains constant, but activity varies with cell cycle phase
- CDK protein abundance remains constant, but activity varies with cell cycle phase
- Activity of CDKs fluctuates / oscillates during the cell cycle, propel the cell cycle forward and create abrupt transitions between different phases
13
Q
How is CDK controlled by cyclin binding
A
- Cyclin + CDK = function
- CDK must be attached to cyclin to function, cyclin tethers target protein so CDK can phosphorylate it
14
Q
How is CDK controlled by phosphorylation
A
- Phosphorylation initiates a chain of events, activation of specific transcription factors (TF)
- TFs promote transcription of certain genes whose products are required for the next stage of the cell cycle
15
Q
How is CDK controlled by inhibitors
A
- Checkpoints activate proteins that inhibit protein kinase activity
- If damaged cell is identified CDK-cyclin complexes stop phosphorylating target proteins
16
Q
How is cell death achieved
A
- Apoptosis: Programmed cell death, eliminate damaged cells / those only needed temporarily
- Necrosis: Uncontrolled cell death, uncontrolled and damages the surrounding tissue
17
Q
Describe chromosome structure
A
- DNA packaged into protein complexes called chromosomes
- Homologous chromosomes undergo replication to form sister chromatids
- Kinetochore: Microtubule binding structure, one per chromatid, either side of centromere
18
Q
Describe the mechanisms of apoptosis
A
- Double strand breaks, stalled replication forks, DNA mismatches / nucleotide damage
- Activate ATM (SS DNA) / ATR (DS DNA) protein kinases
- Active ATM / ATR activate CHK1 / CHK2 protein kinases (do 3 things)
- Induce DNA repair machinery
- Cause CC arrest by inhibiting CDC25
- Activate p53 (tutor suppressor gene), induces cell cycle arrest by activating CKI p21 or severe damage activate apoptosis
HLTH2210
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