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M-checkpoint
G2 Checkpoint
1. Controls entry to mitosis
2. DNA replication assessed
3. Full genome must be present
to allow copy for each
daughter cell
There are a number of key stages to the cell cycle at which point it can be
terminated if necessary:-
G1 check point –
• The cell must be of sufficient size
• DNA must not be damaged
• Environment must be favourable
• Growth factors ( signals from other cells) must be present
• All conditions met – Triggers ‘S’ phase
G2 Checkpoint
• DNA replication assessed and full genome must be present
• Cell must be big enough to support cell division
• All conditions met - entry to mitosis
M check point • At the end of metaphase
•
separation of chromosomes must be successful
• All conditions met - Cytokinesis takes place
G1 checkpoint
• Signalling molecules from other cells known as ‘growth factors’
trigger the production of molecules known as cyclins – the
concentration of these molecules rises at checkpoints if this
happens
• Cyclins bind to kinase enzymes known as CdK or cyclin
dependent kinases forming cyclin-CdK complex
•Cyclin-Cdk complex activates key proteins by phosphorylation
Growth factors
Example – Control of G2 checkpoint
• G2 cyclin levels build up and bind to kinase enzymes called
cyclin dependent kinases or Cdk
•Cdk plus M2 cyclin forms active complex called mitosis
promoting factor or MPF
• MPF starts mitosis which continues up to metaphase i.e. The
chromosomes are lined up on the equator
Progression beyond G2
checkpoint involves activation of
cyclin dependent kinase (Cdk)
by G2 cyclins.
Complex is called Mitosis
Promoting Factor (MPF)
Increased concentration of MPF
causes
• chromosomes to condense
• Nuclear membrane breakdown
•Mitotic spindles form and
chromosomes move to the equator
The concentration of MPK does not change but its
activity rises and falls to to changes in the levels of
G2 cyclin. Click here for animation
M checkpoint
M-checkpoint means
metaphase checkpoint
•Spindle fibres must
be attached to
chromosomes
• Triggers separation
of daughter
chromosomes and
then cytokinesis
•Mitotic cyclin is
broken down to allow
further cycles
The cell cycle is under genetic control. There are two groups of
genes involves :• Proliferation genes or proto-oncogenes – These switch on the
process of mitosis by coding for proteins that promote cell
division e.g. MPF
These are dominant genes and a single mutation may turn them
into oncogenes, starting uncontrolled cell division
Oncogenes are mutated genes where there is a ‘gain-of-function
Oncogenes promote cell division by the overproduction of a
stimulatory protein; such mutations can be at any level in
signalling and transduction.
• Anti-proliferation genes – These are also known as tumour
suppressor genes or anti-oncogenes and are involved in
restricting cell division
• Tumour-suppressor genes, such as the p53 gene, act at
checkpoints; they generate proteins that block progress through
the cell cycle when conditions are not met.
• When tumour suppressor genes mutate there is ‘loss-offunction’.
• Loss of function at these points allows cells to divide though
damaged and unrepaired
• Two copies of the antiproliferation gene have to mutate before
a tumour starts to develop as they are recessive in nature
For nice game on cell cycle click here