1. Unit 1 Cell and Molecular Biology Section 2 Cell cycle, cell growth and differentiation

2. The cell cycle The cell cycle, or mitosis, is the process by which new cells are produced for growth. All cells resulting from this process are identical to each other and the parent cell The cycle has 4 main stages as follows :- G1 – Cell growth and synthesis of organelles S – DNA replication G2 - Cell growth and synthesis of organelles M – Cell division

3. Four Phases of Cell Division Cell growth and synthesis of organelles Cell growth and synthesis of organelles DNA replication

4. The stages G1, S and G2 are collectively known as interphase. The M phase or cell division phase is known as the mitotic phase. Mitosis has a number of stages as shown below:

5. Cell Division and the Cell Cycle Nuclear division is controlled by microtubules which form the spindle fibres and move chromosomes - stages 1-5 Cytokinesis is controlled by actin fibres which split the cytoplasm in two - stage 6

6. Stages of Mitosis StageDescription ProphaseNo distinct chromosome. Nuclear envelope intact PrometaphaseChromosome become visible. Nucleus breaks down MetaphaseChromosomes line up across the centre of cell ( equator) AnaphaseChromosomes divide into chromatids which are pulled to opposite poles by spindle fibres. These are made of microtubules and radiate from the centrosome. TelophaseDaughter chromosomes ( chromatids) reach opposite poles and begin to de-condense CytokinesisCell divides into two by contraction of actin fibres

7. Interphase Follows the M phase and involves cell growth and DNA replication. Made up of G1, S and G2

8. Mitosis - Prophase The replicated chromosomes each consisting of two closely associated sister chromatids condense Outside the nucleus the mitotic spindle assembles between the two centrosomes which have replicated and moved apart.

9. Mitosis - Prometaphase The nuclear envelope suddenly breaks down Chromosomes attach to the spindle microtubules via structures known as kinetochores Chromosomes start to actively move

10. Mitosis – Metaphase The chromosomes are moved to the equator by the spindle fibres The kinetochores of all chromosomes align on the equator, midway between the poles at a structure known as the metaphase plate The paired microtubules attached to each chromosome attach to opposite poles of the spindle

11. Mitosis - Anaphase The paired chromatids from each chromosome separate to form two sister chromatids. Daughter chromosomes are pulled to opposite poles by the simultaneous shortening and lengthening of microtubules

12. Mitosis - Telophase The two sets of daughter chromosomes arrive at the poles A new nuclear envelope reassembles around each set forming to separate daughter nuclei and marking the end of Mitosis

13. Cytokinesis In animal cells the cytoplasm is divided into two by a contractile ring of actin and myosin which pinches in the cell to create two daughter cells.

14. Cytokinesis cont… In plants Membrane vesicles spread across the equator of the cell They merge to form plasma membrane The new membranes lay down the cell wall between the two cells Activity – Read Dart Pg 9-14 - Look at web animation (www.biozone.co.uk/links.html)

15. Cell Cycle There are 3 checkpoints in the cell cycle CK

16. Control of cell cycle G1 Checkpoint End of the G1 phase – the cell size is assessed. If large enough the cell enters S-phase. The cell is usually pushed past this point by signals (growth factors) from outside the cell. If conditions are met DNA replication enzymes called polymerase are transcribed to allow S- phase to begin

17. If conditions are not met Cells don’t divide and remin in G0 Many mature cells e.g. nerve cells, skeletal muscle cells, RBC’s don’t divide. G2 Checkpoint DNA replication success is monitored If replication is successful DNA polymerase enzymes are deactivated Metaphase enzymes are activated If replication is unsuccessful Any cell with unreplicated or damaged DNA that cant be repaired is destroyed (apoptosis = cell suicide)

18. Control of cell cycle - MPF Mitosis (maturation) Promoting Factor (MPF) Promotes transition of G 2 to M phase Acts as a catalyst for the conversion of metaphase enzymes from an inactive to an active state (by phosphorylation)

19. M Checkpoint Occurs during metaphase Checks the spindle has assembled properly All chromosomes are attached properly (by the kinetochores If conditions are met Metaphase enzymes are deactivated Anaphase enzymes are activated

20. Abnormal cell division: Cancer Cancer cells by-pass normal cell control mechanisms. As a result they divide uncontrollably to form lumps of tissue (tumours) that no longer carry out their function.

21. Mutation to Proliferation Genes Normal proliferation genes are called Proto-oncogenes During normal cell division proto-oncogenes code for proteins (e.g. growth factors) that promote cell division Mutated Proliferation genes are called oncogenes Oncogenes act to produce cells that are not required. E.g. Produce a protein which triggers a response in the cell as if growth factors are present Over production of growth factors

22. Oncogenes are dominant Only 1 gene in the pair of alleles needs to mutate for it to have an effect. Mutations in several different genes are usually required for cancer to develop.

23. Mutation to Anti-proliferation genes (AKA Tumour Suppressor Genes) Normal Anti-proliferation Genes Switch off cell division when something goes wrong If the cell is damaged beyond repair apoptosis occurs Mutations to Anti-proliferation Genes Cause the cell to continue dividing when faulty E.g. p53 is a protein produced by a anti-proliferation gene. It binds to damaged DNA stopping cell division until it is repaired. A mutation to this gene results in a faulty protein and cell division with faulty DNA

24. Mutations to anti-proliferation genes are recessive Both alleles of the gene are required to be mutated for mutation to take affect Mutations in several different genes are usually required for cancer to develop Activity – Read Dart Pg 14-17

25. Development An organism starts life as a zygote (single fertilised cell). It undergoes three main stages to develop into an individual 1. Mitotic division to form a group of cells called the blastula. 2. Gastrulation Infolding of the cells to form a cup shape called a gastrula

26. The gastrula has three germ layers Endoderm  Develops into the alimentary canal Ectoderm  Develops into skin and nervous system Mesoderm  Develops into the muscles, skeleton, circulatory system, excretory system 3. Cell division and differentiation (specialisation) results in tissue and organ formation.

27. Differentiation Nearly all cells in an organism have the same DNA Differentiation depends on gene expression (the transcription of a gene into mRNA) i.e. which genes are ‘switched on’ and which genes are ‘switched off’.

28. During development the control of gene expression may be: Temporal (different genes expressed at different times in development) Spatial (cells in different places in the embryo expressing different genes) Example of differentiation to form an organism: Drosophila melanogaster

29. Control of gene expression in bacteria Lac operon (aka Jacob-Monod hypothesis)

31. Stem Cells A stem cell is an undifferentiated cell which can undergo unlimited division to form other cells Source of stem cells Adult e.g. bone marrow Embryonic (from blastula stage ~ 150 cell stage) Cancer cells Umbilical Cord Blood Stem cells have the ability to differentiate, unlike specialised cells

32. Activity – Read Dart Pg 18-20 Web animations from Biozone website http://www.sumanasinc.com/webcontent/anisam ples/nonmajorsbiology/stemcells.htmlhttp://www.sumanasinc.com/webcontent/anisam ples/nonmajorsbiology/stemcells.html http://www.sumanasinc.com/webcontent/anisam ples/majorsbiology/lacoperon.htmlhttp://www.sumanasinc.com/webcontent/anisam ples/majorsbiology/lacoperon.html http://science.howstuffworks.com/stem-cell.htm