Understanding DNA, Cell Division & Genetics: Lecture Insights

1. biology.ed.ac.uk Genetics LECTURE #11 Winter 2011

2. images.businessweek.com newsgroup.xnview.com ergoindemand.com makeupinstyle.webs.com

3. DNA structure • Nucleotides = monomers of DNA/RNA • Nitrogenous base • Cytosine, Thymine, Adenine or Guanine (C, T, A, G) • Pentose sugar • Ribose • Deoxyribose • Phosphate group biologyjunction.com

4. DNA structure • DNA = Double polynucleotide chain – helix structure. • Chromosome = Single DNA molecule that contains hundreds of genes. • Humans = 23 chromosome pairs. • Gene = A section of DNA that codes for a specific protein. • Humans = 24,000 genes. gene familyhistory101.com

5. Genes • Most of our cells have a full copy of our genome • Trillions of cells = Trillions of copies • Different genes are just active in different cells. wired.com

6. Cell Theory • All living organisms possess 1+ cells • All cells come from other cells • Cell division = the process of making new cells • 25 million divisions per second!

7. Cell Division • All cells divide at some point… embryology.med.unsw.edu.au

8. Cell Division • All cells divide at some point… wwf.panda.org

9. Cell Division • Increased rate of division can be stimulated… anat.ucl.ac.uk

10. Cell Division • Cell division is a robust process! baires.elsur.org amazingstufftome.blogspot.com

11. Cell Division • All cells divide at some point… • Some lose ability to divide • Most neural cells finish dividing while in utero • “Cell degradation” • Other tissues active indefinitely • Bone marrow cells pump out 180 million RBC/minute! hutchings-traductions.com

12. Cell Division • 2 parts • Mitosis = the equal division of a cell’s genome • Cytokinesis = the division of the cytoplasm, membranes and organelles

13. DNA usually in uncondensed form

14. Before cell division, DNA duplicates and condenses

15. DNA packaging • Double helix is tightly wound around histones. • Chromatin =DNA molecule + histonesthat collectively make up one sister chromatid. “protein spools” pair of sister chromatids

16. Human karyotype = 23 chromosome pairs You inherit one full chromosome setfrom each parent Homologouschromosomes = similar in size and content, but not identical.

17. Number of chromosomes varies Amoeba 6 670 B base pairs techeye.net Mywatkinsblog.com starcentral.mbl.edu Homo sapiens 46 3 B base pairs Fruit fly 8 137 M base pairs Paris japonica 40 150 B base pairs

18. Steps of cell division • Two phases (16-24 hours) • Interphase G1, S, G2 • Mitotic phase  mitosis & cytokinesis benbest.com

19. Interphase G1(gap-one) • Normal cell operations and cell growth S (synthesis) • Duplication of chromosomes • Duplication of centrosomes

20. DNAduplication • Both strands serve as templates • Free-floating bases arematched to their partners A linked to T and C linked to G

21. Interphase G1(gap-one) • Normal cell operations and cell growth S (synthesis) • Duplication of chromosomes • Duplication of centrosomes G2(gap-two) • Cytoplasmic growth and preparation for division

22. Mitosis & Cytokinesis • Mitosis = separation of cell’s duplicated chromosomes Prophase Metaphase Anaphase Telophase Images from marric.us

23. Prophase • Replicated DNA condenses • 1/8,000th of original length! • Mitotic spindle begins to form • 2 centrosomes direct spindle fibers • Centrosomes migrate to “poles” • Nuclear membrane disassembles

24. Metaphase • Mitotic spindle is complete • Chromosomes are lined up on metaphase plate • Microtubules attach to centromereson the sister chromatids

25. Anaphase • Sister chromatids separate • Shortening microtubules pull sister chromatids toward opposite poles

26. Telophase • Chromosomes arrive at poles • Chromosomes decondense • Nuclear membranes assembled • Result: At the end of telophase we have onecell containing twonuclei.

27. Cytokinesis • Begins during anaphase • Protein filaments form a ring around the cellular equator • Membrane ring contracts, forms “cleavage furrow” • Cytoplasm contents divided in half

28. Videos! Cartoon animation of Mitosis (good for reviewing!) http://www.youtube.com/watch?v=7hQ5xXJSmK4 Excellent video of a lung cell dividing http://www.youtube.com/watch?v=9A3jZYnzlpQ

29. Modeling Mitosis Activity Two sister chromatids (identical) Homologous chromosomes 1 mom, 1 dad

30. Plant cell cytokinesis • Cell wall means makes “pinching” impossible • New cell wall and plasma membrane form by fusion of vesicles. • “Cell plate” is formed

31. Plant cell division

32. Labeling the stages of mitosis

33. Cancer

34. What is cancer? • Uncontrolled cell division • Stems from multiple genetic failures: • Oncogenes=“Stuck accelerator” • Mechanisms that signal division are hyperactive • Tumor suppressor = “Failed brakes” • Mechanisms that suppress division don’t work

35. Closer look at division • Extracellular signal prompts cell division • A protein “growth factor” binds to the outside of a cell • Sets off a cascade of chemical reactions within the cell • Ras protein is turned on • A mutated Rasis “stuck” on … not cancer yet…

36. “The Guardian of the Genome” • p53 (protein 53) is one tumor-suppressor gene • p53levels rise in the presence of certain mutations

37. Mutation build-up initiates p53 • Osmotic shock  Drinking DI water • Ionizing radiation  X-rays • UV radiation  Sunburn • Toxins  Cigarette smoke • Viruses labandscience.com fossumfamilydentalcare.com wellsphere.com

38. “The Guardian of the Genome” • What p53does… • Activate DNA repair mechanisms • Pause cell cycle • Often before S phase • Induce apoptosis (PCD)

39. Checkpoints • In a cell with a ras oncogene, p53can still halt unchecked cell division Cancer = creation of an oncogeneAND failure of the tumor suppressors • Ras (30%) and p53 (50%) present in most cancers • Often additional mutations too • Typically elderly who get cancer

40. Cancer Treatments • Make a detailed, illustrated list of cell division steps • Formulate all places where cell division could go wrong

41. For next time…