Cell Cycle Flashcards
What is the cell cycle?
The cell cycle is a series of events which ends in 2 daughter cells with identical diploid chromosomes.
What is quiescence?
A state in which cells are not dividing.
Also known as G0
Name the stages of mitosis.
- Prophase
- Prometaphase
- Metaphase
- Anaphase
- Telophase
PPMAT
What happens during prophase?
- Chromatin condensation
- Nucleolus disappears
- Centrioles move to poles
What happens during prometaphase?
- Nuclear membrane dissolves
- Chromosomes attach to microtubules and start moving
What happens during metaphase?
- Spindle fibres align the chromosomes along the middle of the cell nucleus (metaphase plate)
What happen during anaphase?
- Paired chromosomes separate and move to opposite sides of the cell
What happens during telophase?
- Chromatids arrive at opposite poles of the cell
- New membranes form around daughter nuclei
- Chromosomes decondense
- Spindle fibres disperse
What are the stages of the cell cycle?
- G1
- S
- G2
- M
OR
Interphase and M phase
What happens during G1?
- Monitor external environment (mitogen dependent)
- Cells grow in size and prepare to undergo DNA synthesis
- Commitment to divide
What happens during S?
Synthesis of DNA
What happens during G2?
- Cells grow in size
- Duplication of organelles
- Preparing for mitosis
What happens during M?
- Mitosis (PPMAT)
- Cleavage of cell to produce daughter cells
What are CDKs?
Cyclin-dependent kinases:
- they regulate progression through the cell cycle - they are made up of serine/threonine kinases - their activity is tightly regulated by cycling, CKIs and phosphorylation/dephosphorylation
What are cyclins?
- Activator proteins that are up or down regulated depending on the phase of the cell cycle
- Unstable proteins
- Different cyclins are associated with different CDKs
What is MPF?
Maturation Promoting Factor:
- also known as CDK1-cyclin B - necessary for progression to stage M - nuclear envelope destroyed - chromosome condensation - spindle formation
What are CKIs?
Cyclin-dependent kinase inhibitors:
- small proteins that block cyclin/CDKS activity - inhibit either by forming an inactive complex or acting as a competitive CDK ligand
What are the three families of CKIs?
- p21 CIP
- p27 KIP
- p16 INK
What is the restriction point in the cell cycle?
The point in G1 at which the cell becomes committed to the cell cycle:
- determined by external factors and signals - cyclin D pairs with CDK 4/6 to regulate this
What are checkpoints in the cell cycle?
Cell monitoring:
- favourable external environment (presence of growth factors) - favourable internal environment (sufficient growth) - DNA damage - replication errors - spindle attachment - chromosome integrity
What are 4 checkpoints of the cell cycle?
- Restriction point (G1)
2/3. DNA damage (G1 and G2) - Metaphase checkpoint (M)
Discuss the restriction point
- determines if conditions are favourable to proceed
- irreversibly commits to the cell division process
- external influences (e.g. growth factors) are important in passing this checkpoint:
- sufficient signal —> cell cycle progresses
- insufficient signal —> cell cycle arrests - cell will only pass this checkpoint if it is an appropriate size and has enough energy reserves
- dependent on the accumulation of cyclin D
- occurs 2-3 hours before S phase
- retinoblastoma (RB) acts as a gatekeeper
What are some examples of growth factors and their function?
- Epidermal growth factor (EGF) - re-epithelialisation (keratinocyte proliferation and migration)
- Platelet-derived growth factor (PDGF) - matrix formation ( increased numbers and activity of fibroblasts) / remodelling (production of proteases)
- Vascular endothelial growth factor (VEGF) - angiogenesis (endothelial cell proliferation and migration)
What is retinoblastoma (RB)?
- tumour suppressor protein
- monitors cell size
- RB binds to transcription factor (e.g. E2F) to inhibit proteins being assembled which would allow cell cycle to progress to S stage
- As the cell size increases RB is phosphorylated until it reaches the point of inactivation, releases the E2F which can then turn on the gene which will produce the transition proteins
Discuss the DNA damage checkpoint
- checks for chemical mutagens, radiation, errors in replication
- happens late G1 and late G2 (so before DNA in synthesis and before cell division occurs)
- p53 may be involved to help repair DNA or trigger apoptosis
- p21 may also be involved to halt the cycle and inhibit the activity of the CDK/cyclin complex
- G2 checkpoint ensures all chromosomes have been accurately replicated before mitosis
What is p53?
- transcription factor
- can halt cell cycle (p21) and recruit enzymes to repair DNA damage
- can induce apoptosis if DNA cannot be repaired
What does p21 do?
- halts the cell cycle by binding to and inhibiting the activity of the CDK/cyclin complex
Discuss the spindle (M) checkpoint
- takes place near the end of metaphase
- determines whether all the sister chromatids are correctly attached to the spindle microtubules
- cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to at least 2 spindle fibres arising from the opposite poles of the cell
- important as anaphase is irreversible
- anaphase promoting complex (APC) is inhibited until all chromosomes are securely attached
