G2 Checkpoint 1.Controls entry to mitosis 2. DNA replication assessed 3. Full genome must be present to allow copy for each daughter cell M-checkpoint

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 animationClick here

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 M checkpoint

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-of- function’. 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 hereclick here