Mitosis Flashcards
What are cyclins?
Proteins associated w/ the cycle of cell division
- initiate certain processes of mitosis
They accumulate in diff stages of cell cycle
What do cyclins do?
What happens then?
How are lamins involved?
Bind & activate cyclin dependent kinases (CDKs)
Cyclin-CDKs phosphorylate key players in cell cycle
–> initiates DNA replication
Lamins initiate nuclear envelope breakdown
How are cyclin levels reduced?
Targeted for destruction by ubiquitination
due to APC/C = anaphase promoting complex/cyclosome
What is the goal of mitosis?
To ensure the accurate partitioning of the genome to daughter cells
How many phases are there in mitosis?
What are they?
6
Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis
Briefly, what happens in the replication & separation of the genome?
- Replicate all DNA once only
= S-phase - Divide copies from 1 nucleus into 2
= M-phase
What is PCNA?
= Proliferating Cell Nuclear Antigen
Part of DNA replication complex
- co-factor of DNA pol
Has a speckled texture in S-phase
What is the role of cohesin in DNA replication?
Cohesin rings keep replicated sister chromatids together
- as replication machinery passes the clamps move along & hold chromatids together
How is DNA only replicated once?
Origins of replication fire once per S-phase
- then the Cyclin-CDK complexes are destroyed by APC/C
What happens if the protein that activates APC/C is removed?
Replication origins keep firing
–> cells never enter M-phase
What is the centrosome also known as?
MTOC
= microtubule organising centre
What happens during the dividing of the genome from 1 nucleus into 2?
Process begins in S/G2 phase w/ duplication of centrosome
–> polarisation of microtubules into a bipolar spindle
What are centrosomes?
Centrioles + pericentriolar material (= mass of proteins)
What are centrioles?
Organelles
- Identical to basal body at base of cilia
- replicated in S/G2 phase
What do centrioles do at the start of M-phase?
Pairs of daughters travel to opposite sides of nucleus
What happens in prophase?
- Chromosome condensation begins
- cohesin holds sister chromatids together
- condensins further loop chromatin into tight bundles - Centrosomes move apart & mitotic spindles begin to form
(Nuclear envelope still in tact)
What happens in pro metaphase?
- Condensed chromosomes attach to microtubules
2. Nucleus envelope breaks down
What causes the nuclear envelope to breakdown?
- Phosphorylation of lamins by cyclin B-CDK1
- Envelope fragments form vesicles
- Vesicles contain lamina B, but NOT lamina A/C - Nuclear pore complexes dissemble
What happens in metaphase?
- Sister chromatids line up on metaphase plate (=equator)
- Dynamic instability
- -> microtubules grow slowly & shrink rapidly - Physical force from dynamic MTs orients the mitotic spindle
What is mitotic spindle orientation sensitive to?
What is the orientation important for?
Physical constraints
- reorients when Mts are cut w/ a laser
Tissue patterning
How does mitotic spindle orientation affect the type of cell produced?
In basal layer (stratified epidermis):
Parallel division
–> stem cells
Perpendicular division
–> differentiation
What is the kinetochore?
A protein complex which links chromatin & microtubules
What is the kinetochore made up of?
Structural & signalling proteins:
> CENP-B protein binds 17-bp sequence in centromeric chromatin
> Sensor proteins that monitor attachment to MTs
- can sense tension
What is the Mitotic Checkpoint Complex (MCC)?
The spindle assembly checkpoint
- it inhibits APC when kinetochores are exposed
(prevents separation of duplicated chromosomes until each chromosome is properly attached to the spindle apparatus)
What happens when all kinetochores are attached to the spindles?
APC is released & activated
- -> targets securin (inhibitor of separase) for degradation
- -> separase cleaves cohesin
How are kinetochores involved in a negative feedback loop?
1 exposed kinetochore stops APC
- -> signals amplified through kinases
- -> cancer
What happens in anaphase?
- Cohesin degraded
2. Sister chromatids move to opposite poles
What are the 2 types of anaphase?
Anaphase A:
chromosomes pulled poleward
Anaphase B:
poles pushes & pulled apart
What happens in telophase?
- Nuclear envelope re-forms & assembles around individual chromosomes
- Microtubules bundle &push nuclei apart
- Contractile ring begins to form on midline
- will become cleave furrow
What happens in cytokinesis?
- Contractile ring cinches & pinches
- actin-myosin fibres slide against each other - Mid-body forms at scission point
What happens is cytokinesis fails?
Binucleate cells are produced
- associated w/ cancer
