Cell Cycle Flashcards
Give five reasons as to why different cells divide at different rates
Embryonic vs. Adult Complexity of system Necessity of renewal State of differentiation (some cells e.g neurons never divide) Tumour cells
Why is it important to regulate cell division?
Abnormal mitosis results in:
cell death
mutations in oncogenes and tumour suppression genes
chromosomal instability (loose/gain whole chromosomes during cell division)
Deviation of protein levels of cell cycle regulators
Contact inhibition of growth
Attack machinery that regulates chromosome segregation
What is the cell cycle?
Orderly sequence of events in which a cell duplicates its contents and divides in two
simply: duplication, division + co-ordination
What occurs during the M-phase?
Nuclear division
Cytokinesis (cell division)
What occurs during interphase?
DNA + organelle replication
Protein synthesis
Why is mitosis the most vulnerable period of the cell cycle?
Cells are more likely to be killed (irradiation, heat shock, chemicals)
DNA damage cannot be repaired
Gene transcription silenced- no new proteins
Metabolism slows down
What happen during G0 phase?
Cell cycle machinery dismantled
Functions normally
What happens during G1 phase?
Decision point- is it able to replicate?
What happens during S phase?
Synthesis of DNA/Protein
Replication of all the organelles
What happens during G2 phase?
Another decision point
What do the centrosomes do?
Consists of two centrioles, barrels of nine triplet microtubules
Microtubules organising centre
Duplicate before entering S phase
What are the 6 phases of Mitosis?
Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis
What happens during prophase I?
Condensation of chromatin
Strong and packed so the chromosomes can move without too much damage
What is a condensed chromosome made up of?
2 sister chromatids each with a kinetochore
Attached by centromere
What happens during prophase II?
Duplicated centrosomes migrate to opposite sides of the nucleus and organise the assembly of spindle microtubules
Mitotic spindle from outside nucleus between the 2 centrosomes
What is the spindle?
Radial microtubule arrays from around each centrosome
They grow until they meet in the centre
Polar microtubules form
What happens during prometaphase I?
Chromosome aligned at equator of the spindle Breakdown of nuclear envelope
Spindle formation largely complete
Attachment of chromosomes to spindle via kinetochores
What happens during prometaphase II?
Microtubule from opposite pole is captured by sister kinetochore
Chromosomes attached to each pole conger to the middle
Chromosomes slides rapidly towards centre along microtubules
What happens during Anaphase A?
Cohesin, which holds sister chromatids together, breaks down
Microtubules shorten
Daughter chromosomes pulled towards opposite poles
What happens during Anaphase B?
Daughter chromosomes migrate towards poles
Spindle poles migrate apart
What happens during telophase?
Daughter chromosome arrive at spindle
Nuclear envelope reassembles
Assembly of contractile ring that separates the two cells
What happens during cytokinesis?
Ring contracts
Midbody (remnants from microtubules that coordinated migration of chromosomes) begins to form
Cells divide
What happens during the transition out of metaphase?
Spindle assembly checkpoint
Make sure all chromatids are bound to a microtubules
And that the microtubules are from different poles
How does the cell communicate that the checks have been completed?
Each sister chromatid needs to signal
Proteins (CENP-E and BUB protein kinases) dissociate from kinetochore when chromosomes are properly attached.
How may aneuploidy occur?
Mis-attachment of microtubules to kinetochores
Aberrant centrosome/DNA replication (multiple rounds of replication)
What happens of the cell is not big enough or their is DNA damage?
- Cell cycle arrest
- at check points (G1 and spindle check point)
- can be temporary (following DNA repair) - Programmes apoptosis
- DNA damage too great cannot be repaired
- Chromosomal abnormalities
- Toxic agents
How can tumour cells avoid check points?
Growth factors at G1 checkpoint induces hyper proliferation
May block G2 checkpoint, mitosis started when cell is not ready
Block Metaphase checkpoint
How else may tumours deregulate cells?
Block exit from cell cycle into G0 phase
Cells repeat cycle immediately
What triggers a cell to enter the cell cycle and divide?
Growth factors
What happens during a signalling cascade?
Réponse to extracellular factors
Signal amplification
Signal integration
Modulation by other pathways
What happens during protein kinase cascades?
Sequence of phosphorylation and activation of subsequent kinases
Signal reversed by phosphotases
Leads to amplification, diversification and opportunity fro regulation
What dis c-Myc protein do?
Transcription factor
Peaks when growth factors are present
It is an oncogene- over expressed in many tumour cells
What are cyclin-dependent kinases?
Present in proliferating cells throughout cycle
Activity regulated by interaction of cyclins and phophorylation
4 types: 1,2,4+6
What do cyclins do?
4 types: A,B,D+E
Transiently expressed at specific points in cell cycle
Regulated at level of expression
Synthesised then degraded
