Cell & Molecular Biology

Control of the Cell Cycle

G2 Checkpoint1. Controls entry to mitosis2. DNA replication assessed3. Full genome must be

present to allow copy for each daughter cell

M-checkpoint

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

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.

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

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

Abnormal Cell Division: Cancer

The cell cycle is under genetic control. There are two groups of genes involves:

Proliferation & Anti-proliferation Genes

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.

•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 here

Anti-proliferation Genes

Essay question due Friday

Write notes on cell cycle and control under the following headings.

i)Interphase (5)ii)Mitosis (5)iii)Mutations (5)