Chapter 8

1. Chapter 8 The Cell Cycle

2. The Life of a Eukaryotic Cell • The ability of organisms to reproduce best distinguishes living things from nonliving matter • The continuity of life is based upon the reproduction of cells, or cell division

4. In unicellular organisms, division of one cell reproduces the entireorganism • Ex. Yeast cells, amoeba • Multicellular organisms begin as a single fertilized egg cell that will go through many cycles of division • Multicellular organisms depend on cell division for: • Development from a fertilized cell • Growth • Repair • Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division

5. LE 12-2 100 µm 200 µm 20 µm Reproduction Growth and development Tissue renewal

6. Cell division results in genetically identical daughter cells • Cells duplicate their genetic material before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA • A dividing cell duplicates its DNA, allocates the two copies to opposite ends of the cell, and only then splits into daughter cells

7. Chromosomes: Cellular Organization of the Genetic Material • A cell’s endowment of DNA (its genetic information) is called its genome • DNA molecules in a cell are packaged into chromosomes

8. Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus • Ex. Human……. 46 • Alligator…… 32 • Amoeba ……. 50 • Corn………… 20

9. Somatic (nonreproductive, also called autosomal) cells have two complete sets of chromosomes • Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells (one complete set)

10. Chromosomes • Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein (histones) that condenses during cell division • Bacteria typically contain one singlecircular chromosome • When cell prepare to divide: • Chromatinchromosomes • Does this by: • chromatin duplicates ( DNA replication) creating a complete second copy of the DNA strand • strands begin to coil tightly until a rod shaped chromatid is formed

11. Structure of Chromosomes

12. LE 12-3 25 µm

13. Distribution of Chromosomes During Cell Division • In preparation for cell division, DNA is replicated and the chromosomes condense • Each duplicated chromosome has two sister chromatids, which separate during cell division • The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached

14. LE 12-4 0.5 µm Chromosome duplication (including DNA synthesis) Centromere Sister chromatids Separation of sister chromatids Centromeres Sister chromatids

15. Human and animal chromosomes are categorized as either • Sex chromosomes: in humans, X and Y. (Human females=XX; males=XY) • Autosomes: all of the other chromosomes • Humans have two sex chromosomes and 44autosomes for a total of 46

16. In sexually reproducing organisms, chromosomes occur in pairs • Homologous chromosomes or homologs: • Each member of a pair; they are the same size, shape, and carry genes for the same trait, but may have different forms of the gene.

17. A cell containing homologous pairs is called • Diploid = 2N, where N = the number of different kinds of chromosomes. • Ex. The 2N, or diploid number of chromosomes for humans = 46, where N=23 in regular body cells (not sperm or egg) • Haploid = 1N, where only one member of a pair is present. • Ex. 1N or haploid number of chromosomes for humans = 23 (sex cells, sperm and egg)

18. Karyotype • A diagram of all 46 human chromosomes is shown on a karyotype • Karyotypes are can be used to diagnose a chromosomal abnormality in a child • Mistakes in chromosome number may result in a genetic disorder

19. Normal Human Karyotype

20. Chromosomal Abnormalities • Deletion: a piece of a chromosome is lost • Inversion: a segment flips around and reattaches • Translocation: a piece from one chromosomes attaches to another • Duplication: a segment doubles itself • Nondisjunction: failure of the two chromatids to separate during division resulting in too few or too many chromosomes

21. Eukaryotic cell division consists of: Mitosis, the division of the nucleus Cytokinesis, the division of the cytoplasm Gametes are produced by a variation of cell division called meiosis Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell Phases of Cell Cycle

22. Phases of the Cell Cycle • The cell cycle consists of • Mitotic (M) phase (mitosis and cytokinesis) • Interphase (cell growth and copying of chromosomes in preparation for cell division) • Interphase (about 90% of the cell cycle) can be divided into subphases: • G1 phase (“first gap”) • S phase (“synthesis”) • G2 phase (“second gap”)

23. LE 12-5 INTERPHASE S (DNA synthesis) G1 Mitosis Cytokinesis G2 MITOTIC (M) PHASE

24. Mitosis is conventionally divided into five phases: • Prophase • Prometaphase • Metaphase • Anaphase • Telophase • Cytokinesis is well underway by latetelophase

25. LE 12-6ca G2 OF INTERPHASE PROPHASE PROMETAPHASE

26. LE 12-6da 10 µm TELOPHASE AND CYTOKINESIS METAPHASE ANAPHASE

27. Video: Animal Mitosis Video: Sea Urchin (time lapse) Animation: Mitosis (All Phases) Animation: Mitosis Overview Animation: Late Interphase Animation: Prophase Animation: Prometaphase Animation: Metaphase Animation: Anaphase Animation: Telophase

28. LE 12-10 Chromatin condensing Nucleus 10 µm Chromosomes Cell plate Nucleolus Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelope will fragment. Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is starting to form. Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divide the cytoplasm in two, is growing toward the perimeter of the parent cell. Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of the cell as their kinetochore micro- tubules shorten.

29. Cytokinesis: A Closer Look • In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow • In plant cells, a cell plate forms during cytokinesis Animation: Cytokinesis

30. LE 12-9a 100 µm Cleavage furrow Daughter cells Contractile ring of microfilaments Cleavage of an animal cell (SEM)

31. LE 12-9b Vesicles forming cell plate Wall of parent cell 1 µm New cell wall Cell plate Daughter cells Cell plate formation in a plant cell (TEM)

32. The Cell Cycle Control System • The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received

33. LE 12-14 G1 checkpoint Control system S G1 G2 M M checkpoint G2 checkpoint

34. For many cells, the G1 checkpoint seems to be the most important one • If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide • If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase

35. LE 12-15 G0 G1 checkpoint G1 G1 If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state. If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

36. The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases • Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks) • The activity of cyclins and Cdksfluctuates during the cell cycle

37. LE12-16a G1 S G2 G1 M M M S G2 MPF activity Cyclin Relative concentration Time Fluctuation of MPF activity and cyclin concentration during the cell cycle

38. LE12-16b G1 Cyclin S Cdk M Degraded cyclin G2 accumulation G2 checkpoint Cdk Cyclin is degraded Cyclin MPF Molecular mechanisms that help regulate the cell cycle

39. Stop and Go Signs: Internal and External Signals at the Checkpoints • An example of an internal signal is that kinetochoresnot attached to spindle microtubules send a molecular signal that delays anaphase • Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide • For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture

40. LE 12-17 Scalpels Petri plate Without PDGF With PDGF Without PDGF With PDGF 10 mm

41. Another example of external signals is density-dependent inhibition, in which crowded cells stop dividing • Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide

42. LE 12-18a Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). 25 µm Normal mammalian cells

43. Cancer • Cancer cells exhibit neitherdensity-dependent inhibition nor anchorage dependence

44. LE 12-18b Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. 25 µm Cancer cells

45. Loss of Cell Cycle Controls in Cancer Cells • Cancer cells do not respond normally to the body’s control mechanisms • Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue • If abnormal cells remain at the original site, the lump is called a benign tumor • Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors

46. LE 12-19 Lymph vessel Tumor Blood vessel Glandular tissue Metastatic tumor Cancer cell A small percentage of cancer cells may survive and establish a new tumor in another part of the body. Cancer cells invade neighboring tissue. A tumor grows from a single cancer cell. Cancer cells spread through lymph and blood vessels to other parts of the body.

47. Genetic Malfunctions related to Cancer • There are three general geneticmalfunctions related to cancer. • The regulation of the cell cycle can be likened to a car that runs properly – starts, stops, and steers properly. • Breakdown in these systems results in uncontrolled cell division - cancer

48. Proto-oncogenes to oncogenes (the gas pedal) • Proto-oncogenes are growth genes (like gas pedals – make a car go) • Mutations in the proto-oncogenes convert them to oncogenes (onco – cancer) • Can be likened to a floored gas pedal – out of control speed

49. Tumor suppressor genes (the brake pedal) • Tumor suppressor genes code for proteins that act as check points and tend to slow or stop rapid cell division. • Mutations in the tumor suppressor genes leads to rapid uncontrolled cell division. • Can be likened to a brake pedal that is missing – out of control speed due to an inability to brake. • Roughly 1/3 of all cancers are due to a defect in a particular tumor suppressor gene called p53.

50. DNA repair genes (the steering wheel) • DNA repair genes scan the double helix and correct mistakes in base pairings (mutations) • Deletions in these DNA repair genes can be likened to a car without a steering wheel – cannot correct the swerving out of control.