Cell Division Flashcards
What is contact inhibition of cell growth?
Cells grow normally by detecting neighbouring cells
What happens during the 3 stages of interphase?
G1: cell ensures it has everything necessary for duplication
S: DNA replication, protein synthesis + replication of organelles
G2: cell checks everything is ready to enter mitosis
What are centrosomes and what is their function?
Consist of 2 centrioles (barrels of 9 triplet microtubules= mother + daughter) at 90 degrees
Microtubule organising center (MTOC)
Miotic spindle
What happens to the centrosomes during G1 and S?
G1: Mother + daughter centrioles separate
S phase: Mother produces another daughter + daughter produces another mother, resulting in the formation of 2 centrosomes
What are the points around the centrosome from which microtubules arise?
Nucleating sites
nucleation is the assembly of microtubules- allows for polymerisation
Describe the condensation of chromatin that takes place during prophase.
Double helices wrap around histones to form beads-on-a-string
This is further compacted to form 30 nm fibres
Its then compacted to form a chromosome scaffold + further wrapped to form a chromosome (1400 nm)
What is a kinetochore?
Protein complexes that are attached to each sister chromatid
important in detecting the attachment of microtubules
Describe the arrangement of centrosomes at the end of prophase. What are they doing here?
On opposite sides of the nucleus.
Organising assembly of spindle microtubules
Miotic spindle forms outside the nucleus between the 2 centrosomes
What is formed when radial microtubule arrays from the two centrosomes meet in the middle?
Polar microtubules
What happens to the sister chromatids as soon as they are captured by microtubule arrays from both centrosomes?
They slide towards the middle of the cell
What are the 3 main types of half-spindle?
Kinetochore microtubule: attached to kinetochores
Polar microtubule: attached to a microtubule array from the other centrosome
Astral microtubule: microtubule originating from a centrosome that does not connect to a kinetochore
What keeps the sister chromatids stuck together?
Cohesin (protein complex)
What happens in anaphase A?
Cohesin is broken down + microtubules shorten so chromatids start moving towards their respective poles
What happens in anaphase B?
Daughter chromatids continue to migrate towards the poles
Centrosomes migrate apart
Describe what happens in telophase.
Daughter chromatids arrive at the pole + nuclear envelope reassembles
Assembly of a contractile ring of actin + myosin filaments where the cell is going to split
The contractile ring squeezes the cell so it divides into 2 daughter cells
Cleavage furrow = where the cell is going to be cleaved
What is the midbody?
Where the actin-myosin contractile ring is formed
Describe how the spindle assembly checkpoint works.
Kinetochore has proteins that emit a signal when the kinetochore is NOT attached to microtubules
When a microtubule attaches to the kinetochore, it stops emitting the signal
At the end of metaphase, want all kinetochores to stop sending signals before proceeding to anaphase
Name two proteins that allow the kinetochores to detect spindle attachment.
CENP-E (senses tension of microtubules)
BUB-protein kinase (dissociates from kinetochores when chromosomes are properly attached to the spindle, then they go on to signal progression to anaphase)
What can cause aneuploidy?
Mitotic checkpoint defect : Mis-attachment of the spindles (chromatids end up at different poles to the ones that they should be at) Aberrant mitosis (production of an abnormal number of centrosomes leads to abnormal division of the chromatids, + abnormal cytokinesis)
Name 4 different types of spindle attachment.
Amphitelic: normal spindle attachment
Syntelic: both kinetochores of sister chromatids are attached to spindles from 1 centrosome
Merotelic: >1 spindle attached to same kinetochore
Monotelic: 1 kinetochore of 1 of the chromatids is attached to a spindle, the other is unattached
Broadly speaking, explain how cell cycle checkpoints can be a target for anti-cancer therapy.
By targeting the cell cycle checkpoints, cancer cells can be arrested in mitosis
Cells are very vulnerable when in mitosis + are more easily killed
Give an example of anti-cancer drugs that target cell cycle checkpoints.
Taxanes + Vinca alkaloids
Alter microtubule dynamics + produce unattached kinetochores, which leads to long-term miotic arrest
What can happen to cells that are held up at a checkpoint?
Undergo DNA repair + then proceed through the cell cycle
If damage is irreparable, they can undergo apoptosis
Where are the main checkpoints within the cell cycle?
During G1
Mitosis entry: Just before mitosis to check for DNA damage
Metaphase-anaphase checkpoint (spindle assembly checkpoint, checks alignment of chromosomes)
Why do different cells divide at different rates?
Embryonic divide much faster than adult
Complexity of cell
Necessity for renewal e.g. intestine undergoing constant renewal
State of differentiation e.g. some never divide- neurones
Tumours lose the ability to control proliferation
Why is mitosis the shortest phase of mitosis?
Most vulnerable period Cells more easily killed DNA damage during can't be repaired Gene transcription is silenced Metabolism is reduced, energy focused on division
List the 6 phases of mitosis
Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis
In which phase are chromosomes aligned at the equator of the spindle?
Metaphase
What occurs in early pro metaphase?
Breakdown of nuclear membrane
Spindle formation largely complete
Attachment of chromosomes to spindle via kinetochores
What occurs in late pro metaphase?
Microtubule from opposite pole is captured by sister kinetochore
What can inhibition of attachment error-correction mechanism lead to?
Cell divides before chromosomes are aligned
Inviable cells
Apoptosis
What does serine threonine kinase (checkpoint kinase) activation do? Thus, what does inhibition of this cause?
Holds cells in G2 phase until all is ready
Inhibition leads to untimely cell transition to mitosis + cell death
How may tumours effect each checkpoint?
Upregulation of growth factors/ receptors increasing the speed of the cycle
Blockade of entry to mitosis checkpoint, so cell enters mitosis before it is ready
Blockade of alignment checkpoint: causes loss/ gain of chromosomes
Blockade of exit from cycle
How do growth factors activate a cell? What does receptor activation trigger?
GFs are dimeric, bind to 2 receptors.
Once in close proximity, the tyrosine kinase domains cross phosphorylate each other, becoming activated
Triggers kinase cascades + binding of adapter proteins
How does phosphorylation alter protein function?
Causes conformational change leading to change in activity
Creates docking site for another protein
What is the significance of protein kinase cascades?
Leads to signal amplification, diversification + opportunity for regulation
What is phosphorylation reversed by?
Phosphatases
