Cell Cycle Flashcards
What does the rate of cell division depend on
Embryonic vs adult cells Complexity of system Necessity for renewal State of differentiation Tumour cells
What is the relevance of the appropriate regulation of the cell division
Premature, aberrant mitosis results in cell death
Most tumours are aneuploid (have an abnormal chromosome number as well as content)
Tumour cells lose contact inhibition of growth, where if a cell is touching other cells (has no space to reproduce) then it won’t.
Why is mitosis the most vulnerable period of the cell cycle
Cells are more easily killed (irradiation, heat shock, chemicals)
DNA damage can not be repaired
no genes are being transcribed, as they’re being packed and separated
very little other metabolism is occurring due to the energy requirements of mitosis
What are the stages of the cell cycle
M phase - Mitosis
Interphase G0 - cell cycle machinery dismantled G1 - decision point S - synthesis of DNA/protein G2 - Decision point
What occurs in the S phase
Replication for division:
DNA replication
Protein synthesis: initiation of translation and elongation increased; capacity is also increased
Replication of organelles (centrosomes, mitochondria, Golgi, etc)
What is important in the S phase replication of mitochondria
Needs to coordinate with replication of mitochondrial DNA
Describe the centrosome and its functions
Consists of two centrioles (barrels of 9 triplet microtubules)
origin of all the microtubules of the mitotic spindle
Describe the life cycle of centrosomes during mitosis
During late G1, the centrioles split and each one later goes on to duplicate, forming its own centrosome. This is a prerequisite for mitosis.
What are the phases of mitosis
(Interphase) Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis
What occurs during prophase
Condensation of chromatin
Each condensed chromosome consists of 2 sister chromatids joined at the centromere, each with a kinetochore
Nuclear envelope begins to break down
What occurs during late prophase
- Duplicated centrosomes migrate to opposite sides of the nucleus
- Centrosomes organise the assembly of spindle microtubules
- Radial microtubule arrays (ASTERS) form around each centrosome (microtubule organizing centers - MTOC)
- Polar microtubule formation
What is the difference between polar and astral microtubules
Radial microtubules from each centrosome which meet in the middle of the cell form polar microtubules.
The ones that don’t go towards the middle are called astral microtubules.
What occurs during early pro metaphase
- Breakdown of nuclear membrane
- Spindle formation largely complete
- Attachment of chromosomes to spindle via kinetochores (centromere region of chromosome)
What occurs during late pro metaphase
- Chromosome slides rapidly towards center along microtubules
- Chromosomes attached to each pole congress to the middle
- Microtubule from opposite pole is captured by sister kinetochore
What occurs during metaphase
Chromosomes aligned at equator of the spindle First checkpoint (spindle assembly/mitotic/M checkpoint)
What occurs during anaphase
Paired chromatids separate to form two daughter chromosomes
Anaphase A and B
What occurs during anaphase A
- Breakdown cohesin (which was holding the sister chromatids together)
- Microtubules get shorter
- Daughter chromosomes pulled toward opposite spindle poles
What occurs during anaphase B
- Daughter chromosomes migrate towards poles
2. Centrosomes also migrate apart
What occurs during telophase
- Daughter chromosomes arrive at spindle
- Nuclear envelope reassembles at each pole
- Assembly of contractile/myosin ring to create a cleavage furrow
- As the ring contracts, a new membrane Is inserted
What is the midbody
where the leftover microtubules overlap after telophase
What important regulatory event occurs during the transition out of metaphase
Spindle assembly checkpoint
Sensed completion of chromosome alignment and spindle assembly (minters kinetochore activity)
When all dissociated, anaphase proceeds.
What does the spindle assembly checkpoint require
CENP-E
BUB protein kinases
BUBs dissociate from kinetochore when chromosomes are properly attached to the spindle
CENP-E (centromere protein E) checks that all the chromosomes are connected to it
What during mitosis can lead to aneuploidy
Mis-attachment of microtubules to kinetochores
Aberrant centrosome/DNA duplication
What are the different ways in which there can be mis-attachment of microtubules to kinetochores
Cohesion defects/synthetic attachment Merotelic attachment (chromatid attached to both centrosomes via both sides of kinetochore) which would not produce a checkpoint signal
Describe the use of checkpoint kinase in anti-cancer therapy
Induces gross chromosome mis-segregation
Holds cells in G2 phase until they are all ready
Inhibition leads to untimely cell transition to mitosis
Knases - CHKE1 and CHKE2
Describe the use of taxanes and vinca alkaloids in anti-cancer therapy
Induces gross chromosome mis-segregation in breast and ovarian cancers
Alters microtubule dynamics
Produces unattached kinetochores
Causes long-term mitotic arrest.
What happens when and error occurs during the cell cycle
Cell cycle arrest
Programmed cell death
Describe cell cycle arrest when there is an error during the cell cycle
At check points (G1 and spindle check point)
Can be temporary (i.e. following DNA repair)
Describe programmed cell death when there is an error during the cell cycle
DNA damage too great and cannot be repaired
Chromosomal abnormalities
Toxic agents
What happens when a cell is not simulated to enter the cell cycle
In the absence of stimulus, cells go into Go (quiescent phase)
Most cells in the body which are differentiated to perform specific functions
Cells are not dormant, but are non-dividing
What does exit from G0 require
Growth factors and intracellular signalling cascades
Describe the signalling cascades
Response to extracellular factors Signal amplification Signal integration Modulation by other pathways Regulation of divergent responses
What triggers a cell to enter the cell cycle and divide?
Signalling by peptide growth factors: Ligand binds and activates the receptor
Ligands: Epidermal growth factor (EGF); Platelet-derived growth factor (PDGF)
Describe the receptors involved in signalling cascades and what they do in the presence of ligand
Respective receptors found as monomeric, inactive state
Receptor Protein Tyrosine Kinase (RPTK)
Receptors form dimers
Activated by phosphorylation
Describe protein phosphorylation and which amino acids are targeted
Transfer of phosphate from ATP to a hydroxyl groups
Serine
Threonine
Tyrosine
What are the ways in which an added phosphate group (-ve charge) can alter protein function
Causing a change in shape (conformation) leading to change in activity (+ve or –ve)
Creating a docking site for another protein
What occurs when there is signalling by peptide growth factors during receptor activation
Triggers kinase cascades and binding of adapter proteins
What is syntelic attachment
kinetochore is attached to microtubules of the same centrosome. Both sister chromatids end up at the same pole
What is monotelic attachment
one kinetochore is attached by a microtubule
What is merotellic attachment
more than on microtubule attaching to the same kinetochore, leads to loss of sister chromatid
