1. Cell division Chapter 10 Genes and Development

2. Fig. 10.1-1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Bacterial cell Bacterial chromosome: Double-stranded DNA Origin of replication

3. Fig. 10.1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Bacterial cell Septum Bacterial chromosome: Double-stranded DNA Origin of replication

4. Fig. 10.2

5. Fig. 10.3a Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Septum FtsZ protein Chromosome Prokaryotes No nucleus, usually have single circular chromosome. After DNA is replicated, it is partitioned in the cell. After cell elongation, FtsZ protein assembles into a ring and facilitates septation and cell division.

6. Fig. 10.3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Septum FtsZ protein Chromosome Microtubule Nucleus Kinetochore microtubule CentriolesKinetochore Polar microtubule Spindle pole body Kinetochore microtubule Centriole ProkaryotesSome ProtistsOther ProtistsAnimals Kinetochore microtubule Polar microtubule No nucleus, usually have single circular chromosome. After DNA is replicated, it is partitioned in the cell. After cell elongation, FtsZ protein assembles into a ring and facilitates septation and cell division. Nucleus present and nuclear envelope remains intact during cell division. Chromosomes line up. Microtubule fibers pass through tunnels in the nuclear membrane and set up an axis for separation of replicated chromosomes, and cell division. A spindle of micro- tubules forms between two pairs of centrioles at opposite ends of the cell. The spindle passes through one tunnel in the intact nuclear envelope. Kinetochore microtubules form between kinetochores on the chromosomes and the spindle poles and pull the chromo- somes to each pole. Nuclear envelope remains intact; spindle microtubules form inside the nucleus between spindle pole bodies. A single kinetochore microtubule attaches to each chromosome and pulls each to a pole. Spindle microtubules begin to form between centrioles outside of nucleus. Centrioles move to the poles and the nuclear envelope breaks down. Kinetochore microtubules attach kinetochores of chromosomes to spindle poles. Polar microtubules extend toward the center of the cell and overlap. Yeasts Central spindle of microtubules Fragments of nuclear envelope

7. Table 10.1

8. Fig. 10.5-1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromosome

9. Fig. 10.5-2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ChromosomeRosettes of Chromatin Loops Scaffold protein

10. Fig. 10.5-3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ChromosomeRosettes of Chromatin LoopsChromatin Loop Chromatin loop Scaffold protein Scaffold protein

11. Fig. 10.5-4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ChromosomeRosettes of Chromatin LoopsChromatin LoopSolenoid Chromatin loop Scaffold protein Scaffold protein

12. Fig. 10.5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ChromosomeRosettes of Chromatin LoopsChromatin LoopSolenoid Nucleosome Histone core Chromatin loop Scaffold protein Scaffold protein DNA DNA Double Helix (duplex)

13. Animation of DNA coiling DNA coiling and cells dividing

14. Fig. 10.6

15. Fig. 10.7 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Homologous chromosomes Sister chromatids Centromere Replication Kinetochore Kinetochores Cohesin proteins Centromere

16. Fig. 10.8 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. G1G1 G2G2 S Interphase Mitosis M Phase Cytokinesis M Phase G2G2 S G1G1 Metaphase Prophase Anaphase Telophase Prometaphase Cell cycle

17. Fig. 10.9 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromatid Kinetochore Cohesin proteins Centromere region of chromosome Metaphase chromosome Kinetochore microtubules

18. Fig. 10.10 Red = Cohesin Green = Kinetochore Blue = Chromosome

19. Fig. 10.11a Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Andrew S. Bajer, University of Oregon INTERPHASE G 2 Nucleus Nucleolus Aster 80 µm Centrioles (replicated; animal cells only) Nuclear membrane DN A has been replicated Centrioles replicate (animal cells) Cell prepares for division Chromatin (replicated)

20. Fig. 10.11b Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Prophase 80 µm Chromosomes condense and become visible Chromosomes appear as two sister chromatids held together at the centromere Cytoskeleton is disassembled: spindle begins to form Golgi and ER are dispersed Nuclear envelope breaks down Mitotic spindle beginning to form Condensed chromosomes © Andrew S. Bajer, University of Oregon MITOSIS

21. Prometaphase 80 µm Chromosomes attach to microtubules at the kinetochores Each chromosome is oriented such that the kinetochores of sister chromatids are attached to microtubules from opposite poles. Chromosomes move to equator of the cell Centromere and kinetochore Mitotic spindle Fig. 10.11c Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Andrew S. Bajer, University of Oregon MITOSIS

22. Metaphase All chromosomes are aligned at equator of the cell, called the metaphase plate Chromosomes are attached to opposite poles and are under tension Polar microtubule 80 µm Chromosomes aligned on metaphase plate Kinetochore microtubule Fig. 10.11d Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Andrew S. Bajer, University of Oregon MITOSIS

23. Fig. 10.12 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Centrioles Sister chromatids Aster 57 µm Kinetochore microtubule Metaphase plate Polar microtubule © Andrew S. Bajer, University of Oregon

24. Anaphase Chromosomes Proteins holding centromeres of sister chromatids are degraded, freeing individual chromosomes Chromosomes are pulled to opposite poles (anaphase A) Spindle poles move apart (anaphase B) Kinetochore microtubule 80 µm Polar microtubule Fig. 10.11e Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Andrew S. Bajer, University of Oregon MITOSIS

25. Fig. 10.13 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metaphase Pole 2 µm Overlapping microtubules Late Anaphase Overlapping microtubules © Dr. Jeremy Pickett-Heaps

26. Telophase Polar microtubule Nucleus reforming Chromosomes are clustered at opposite poles and decondense Nuclear envelopes re-form around chromosomes Golgi complex and ER re-form 80 µm Kinetochore microtubule Fig. 10.11f Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Andrew S. Bajer, University of Oregon MITOSIS

27. Fig. 10.11g Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cleavage furrow CYTOKINESIS In animal cells, cleavage furrow forms to divide the cells In plant cells, cell plate forms to divide the cells 80 µm © Andrew S. Bajer, University of Oregon

28. Fig. 10.11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. INTERPHASE G 2 ProphasePrometaphaseMetaphaseAnaphaseTelophase Nucleus Nucleolus Aster Chromosomes Polar microtubule Nucleus reforming Cleavage furrow 80 µm CYTOKINESIS MITOSIS Centrioles (replicated; animal cells only) Nuclear membrane DN A has been replicated Centrioles replicate (animal cells) Cell prepares for division Chromosomes condense and become visible Chromosomes appear as two sister chromatids held together at the centromere Cytoskeleton is disassembled: spindle begins to form Golgi and ER are dispersed Nuclear envelope breaks down Chromosomes attach to microtubules at the kinetochores Each chromosome is oriented such that the kinetochores of sister chromatids are attached to microtubules from opposite poles. Chromosomes move to equator of the cell All chromosomes are aligned at equator of the cell, called the metaphase plate Chromosomes are attached to opposite poles and are under tension Proteins holding centromeres of sister chromatids are degraded, freeing individual chromosomes Chromosomes are pulled to opposite poles (anaphase A) Spindle poles move apart (anaphase B) Chromosomes are clustered at opposite poles and decondense Nuclear envelopes re-form around chromosomes Golgi complex and ER re-form In animal cells, cleavage furrow forms to divide the cells In plant cells, cell plate forms to divide the cells Polar microtubule Kinetochore microtubule Chromatin (replicated) 80 µm Mitotic spindle beginning to form Condensed chromosomes Centromere and kinetochore Mitotic spindle Chromosomes aligned on metaphase plate Kinetochore microtubule Polar microtubule Kinetochore microtubule © Andrew S. Bajer, University of Oregon

29. Fig. 10.14

30. Fig. 10.15 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell wall Nucleus 0.7 µm Vesicles containing membrane components fusing to form cell plate © B.A. Palevits & E.H. Newcomb/BPS/Tom Stack & Associates Plants

31. Fig. 10.16-1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. SCIENTIFIC THINKING Hypothesis: There are positive regulators of mitosis.

32. Fig. 10.16-2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. SCIENTIFIC THINKING Hypothesis: There are positive regulators of mitosis. Prediction: Frog oocytes are arrested in G 2 of meiosis I. They can be induced to mature (undergo meiosis) by progesterone treatment. If maturing oocytes contain a positive regulator of cell division, injection of cytoplasm should induce an immature oocyte to undergo meiosis.

33. Fig. 10.16-4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Remove cytoplasm Arrested oocyteOocyte in meiosis I SCIENTIFIC THINKING Hypothesis: There are positive regulators of mitosis. Prediction: Frog oocytes are arrested in G 2 of meiosis I. They can be induced to mature (undergo meiosis) by progesterone treatment. If maturing oocytes contain a positive regulator of cell division, injection of cytoplasm should induce an immature oocyte to undergo meiosis. Test: Oocytes are induced with progesterone, then cytoplasm from these maturing cells is injected into immature oocytes. Result: Injected oocytes progress G 2 from into meiosis I. Inject cytoplasm Progesterone- treated oocyte

34. Fig. 10.16-5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Remove cytoplasm Arrested oocyteOocyte in meiosis I SCIENTIFIC THINKING Hypothesis: There are positive regulators of mitosis. Prediction: Frog oocytes are arrested in G 2 of meiosis I. They can be induced to mature (undergo meiosis) by progesterone treatment. If maturing oocytes contain a positive regulator of cell division, injection of cytoplasm should induce an immature oocyte to undergo meiosis. Test: Oocytes are induced with progesterone, then cytoplasm from these maturing cells is injected into immature oocytes. Result: Injected oocytes progress G 2 from into meiosis I. Conclusion: The progesterone treatment causes production of a positive regulator of maturation: Maturation Promoting Factor (MPF). Inject cytoplasm Progesterone- treated oocyte

35. Fig. 10.16-7 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Remove cytoplasm Arrested oocyteOocyte in meiosis I M phase cellG 1 phase cellFused cells SCIENTIFIC THINKING Hypothesis: There are positive regulators of mitosis. Prediction: Frog oocytes are arrested in G 2 of meiosis I. They can be induced to mature (undergo meiosis) by progesterone treatment. If maturing oocytes contain a positive regulator of cell division, injection of cytoplasm should induce an immature oocyte to undergo meiosis. Test: Oocytes are induced with progesterone, then cytoplasm from these maturing cells is injected into immature oocytes. Result: Injected oocytes progress G 2 from into meiosis I. Conclusion: The progesterone treatment causes production of a positive regulator of maturation: Maturation Promoting Factor (MPF). Prediction: If mitosis is driven by positive regulators, then cytoplasm from a mitotic cell should cause a G 1 cell to enter mitosis. Test: M phase cells are fused with G1 phase cells, then the nucleus from the G1 phase cell is monitored microscopically. Conclusion: Cytoplasm from M phase cells contains a positive regulator that causes a cell to enter mitosis. Inject cytoplasm Progesterone- treated oocyte

36. Fig. 10.17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. G1G1 SG2G2 MG2G2 MG1G1 SG2G2 M Concentration Low High MPF activity Cyclin

37. Fig. 10.18 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. G2G2 M S G1G1 Spindle checkpointG 2 /M checkpoint G 1 /S checkpoint (Start or restriction point)

38. Fig. 10.19 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cyclin P Cyclin-dependent kinase (Cdk) P

39. Fig. 10.20 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Growth factors Size of cell G2G2 M S G1G1 Spindle Checkpoint APCCdc2/Mitotic Cyclin Chromosomes attached at metaphase plate Replication completed DNA integrity G 2 /M Checkpoint G 1 /S Checkpoint Cdk1/Cyclin B Nutritional state of cell Yeast

40. Fig. 10.21 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Growth factors Size of cell G2G2 M S G1G1 Spindle Checkpoint APCCdk1/Cyclin B Chromosomes attached at metaphase plate Replication completed DNA integrity G 2 /M Checkpoint G 1 /S Checkpoint Cdc2/G 1 Cyclin Nutritional state of cell Animals

41. Fig. 10.22 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nucleus Chromosome RAF MEK ERK E2F Rb P P P P P P P P P P Growth factor Cyclins/ proteins for S phase Cyclins/ proteins for S phase RAF MEK ERK Nucleus Rb E2F Chromosome P P RAS MAP kinase pathway Rb

42. Fig. 10.23-1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1. DNA damage is caused by heat, radiation, or chemicals. 2. Cell division stops, and p53 triggers enzymes to repair damaged region. 3. p53 triggers the destruction of cells damaged beyond repair. p53 allows cells with repaired DNA to divide. DNA repair enzyme p53 protein Normal p53

43. Fig. 10.23 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1. DNA damage is caused by heat, radiation, or chemicals. 2. Cell division stops, and p53 triggers enzymes to repair damaged region. 3. p53 triggers the destruction of cells damaged beyond repair. p53 allows cells with repaired DNA to divide. 1. DNA damage is caused by heat, radiation, or chemicals. 2. The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. 3. Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. DNA repair enzyme Cancer cell p53 protein Normal p53 Abnormal p53 Abnormal p53 protein

44. Fig. 10.24 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Proto-oncogenes Growth factor receptor: more per cell in many breast cancers. Ras protein: activated by mutations in 20–30% of all cancers. Src kinase: activated by mutations in 2–5% of all cancers. Tumor-suppressor Genes Rb protein: mutated in 40% of all cancers. p53 protein: mutated in 50% of all cancers. Cell cycle checkpoints Ras protein Rb protein p53 protein Src kinase