1. Cell & Molecular Biology Control of the Cell Cycle

2. 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

3. G1 checkpoint Multicellular organisms, signalling molecules called ‘growth factors’ from surrounding cells trigger the production of cyclins which increase in concentration at the checkpoints. Cyclins bind to kinase enzymes known as cyclin dependent kinases (CdK) forming cyclin-CdK complex Cyclin-Cdk complex activates key proteins by phosphorylation Growth factors

5. Control of G2 checkpoint G2 cyclin levels build up and bind to kinase enzymes (CdK) CdK plus M2 cyclin forms active protein complex called mitosis promoting factor or MPF. Mitosis Promoting Factor is essential for entry to mitosis.

6. 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

7. Controls entry to anaphase Ensures chromosomes are aligned correctly on equator Ensures daughter cells receive correct number of chromosomes Triggers separation of daughter chromosomes and then cytokinesis M (metaphase) checkpoint

8. Abnormal Cell Division: Cancer The cell cycle is under genetic control. There are two groups of genes involves: Proliferation & Anti-proliferation Genes

9. Proliferation Genes 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 therefore a single mutation would convert them into the mutant type ‘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.

10. These are also known as tumour suppressor genes or anti- oncogenes and are involved in restricting cell division Eg. p53 gene, act at checkpoints by generating proteins that block progress through the cell cycle when conditions are not met. When tumour suppressor genes mutate there is ‘loss-of- function’ allowing damaged or unrepaired cells to divide 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 Anti-proliferation Genes

11. Essay question due Friday Write notes on cell cycle and control under the following headings. i)Interphase(5) ii)Mitosis(5) iii)Mutations(5)