Mitosis

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What is mitosis?

i) Mitosis defined

Process of division in eurkaryotic cells where a parent cell divides to form four diploid daughter cells

Entire cell cycle (including mitosis) = approx. 20 hours

Mitosis takes between 0.5-2 hours out of this 20 to occur

What is the function of mitosis?

Repair damaged tissues

Growth (increase in number) - notably in embryo formation

Immune cell proliferation

Maintenance of function

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Stages of cell cycle

Composed of 4 stages:

G1 phase - G0

S phase

G2 phase

M phase

G1, S & G2 = interphase

Preparing to divide

Cell spends ~90% of its lifetime in this phase

M phase = mitosis phase

Active dividing

i) Cell cycle timing

Varies between cells depending on their function & origin

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Frequency of division

Length of cell cycle varies between cell types

Epithelial cells = short cell cycle (between 10-24 hours)

Liver cells = much longer cell cycle (divide once a year)

Possess ability to temporarily disassemble their cell-cycle control system & then reassemble it when required!

Skeletal muscle cells & mature nerve cells = lost ability to divide

Permanently stuck in G0 phase

Embryonic stem cells = capacity for unlimited proliferation

Have short G1 phase

Lots of cells in S phase

i) What is G0 phase?

When cells stop dividing for a long period of time

If cell does not receive signals telling it to proliferate, it becomes mitotically inactive

Why are cells sent into G0 phase?

Some cells are just waiting until required for reparative growth/normal cell development

Irreversible commitment of cells to a particular fate (i.e. becoming a specialised cell)

i.e. oocytes in females

Some cells are purposely sent into G0 by DDR as protective mechanism

(**See Mol Med lecture DDR & cancer pg. 2)

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G1 phase

What happens in G1 phase?

Interval between mitosis & onset of DNA replication

Cell growth

Cytoplasm increases in volume

RNA & protein synthesis occurs

G1 checkpoint must be passed before cell can enter S phase!

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S phase

What happens during S phase?

Synthesis phase

DNA replication occurs!

i) DNA replication

Weak H bonds between bases broken by DNA helicase

Produces single DNA strands (Template strands) with unpaired bases

Site @ which DNA helix first unwinds = Replication origin

Splitting occurs in both directions

Causes formation of 'replication bubbles' @ end of which = replication forks

2. DNA polymerase travels along single DNA strand & attaches free nucleotides to the 3' end of new strand

Nucleotides can only be added to 3' end

Replication occurs from 5' to 3' end - 'Leading strand'

Lagging strand = other strand being formed in opposite direction to leading

Replication occurs from 5' to 3' end as well

Only occurs in short stretches

Because it must start @ random points in DNA sequence - not from origin of replication like leading strand can!

Short stretches of DNA on lagging strand = Okazaki fragments

Single-strand binding protein temporarily protects the original DNA strand whilst lagging is being formed

DNA ligase sticks Okazaki fragments together

DNA polymerase also proofreads each newly added nucleotide to make sure it is complementary to the template base

If not, nucleotide removed & replaced with correct one

Mutations in this feature = genetic diseases

Each new DNA strand formed consists of 1 original strand & 1 new strand!

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G2 phase

What happens during G2 phase?

Interval between S phase & next mitosis

Cell growth

Some DNA repair

Cell prepares for mitosis

At this point cell contains 2 identical copies of each of 46 chromosomes (sister chromatids)

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M phase

What happens during M phase?

Mitosis!

Broken up into 6 stages:

Prophase

Prometaphase

Metaphase

Anaphase

Telophase

Cytokinesis

1. Prophase

Nucelolus disappears

Chromosomes begin to condense & coil

Requires condensin & DNA topisomerase II

Duplicated centrioles seperate & move to opposite poles of cell

'Spindle-apparatus' of tubulin fibres begins assembling from centrioles

Histones undergo mitosis-specific modifications

2. Prometaphase

Nuclear membrane dissociates

Spindle tubulin fibres extend from each pole & attach to kinetochores

Kinetochores have developed around centromeres of chromosomes

They are attached to the chromosomes

3. Metphase

Chromosomes align at metaphase plate in cell equator

Identical chromatids are attached to spindle fibres from opposite ends of the cell

The same genetic information will be sent to opposite poles of the cell

4. Anaphase

Centromere of each chromosome splits as chromatids are pulled by spindle fibres to opposite sides of cell

Nuclear membrane reassembly commences

92 chromosomes are contained in cell @ end of anaphase

46 on left, 46 on right

Both sets of chromosomes should be identical!

5. Telophase

Nuclear envelope reassembles around each of 2 sets of 46 chromosomes

Chromosomes condense to chromatin

Nucleoli reform

Spindle fibres disappear

Cleavage plane is specified

6. Cytokinesis

Cell membrane contracts around mid-region of cell using actin-myosin filament ring

Creates cleavage furrow

2 new diploid daughter cells have been formed!!!

​​​​​​​They are identical to the original cell they came from!