The Cell Cycle: Stages, Control Checkpoints, and Cell Division

1. CHAPTER 12 THE CELL CYCLE

2. What is the cell cycle? • The cell cycle is a complex set of stages that is highly regulated with checkpoints, which determine the ultimate fate of the eukaryotic cell. Heritable information provides for continuity of life. • In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization.

3. 1855 Rudolf Virchow“Omnis cellula e cellula!” • “Every cell originates from another cell.” • From the observation that only certain cells or groups of cells become sick. • Doctor of anatomic pathology (microscopes). Encouraged his students to “think microscopically” • 1st to recognize leukemia (cancer of the blood or bone marrow)

5. Why do cells divide? • Continuity of life- reproduction. MITOSIS/MEIOSIS • Growth & Development (from single zygote). MITOSIS • Renewal & repair (blood cells, skin cells) MITOSIS • surface:volume ratio (size) • genome:cytoplasmic ratio • hormones/growth factors • age… apoptosis • or don’t… because of contact inhibition

6. REPRODUCTION Amoeba divides to form two cells

7. GROWTH & DEVELOPMENT GROWTH & DEVELOPMENT Sand dollar embryo shortly after fertilization… 1 -> 2 cells

8. Figure 12.1c The functions of cell division: Tissue renewal TISSUE RENEWAL bone marrow cells give rise to blood cells.

9. What must happen before a cell is ready to divide???? The cell must: • grow by producing proteins and cytoplasmic organelles. • duplicate the DNA (chromosomes). • separate replicated chromosome(s) to opposite sides of the cell.

10. CELL DIVISION Prokaryotic vs. Eukaryotic “Binary Fission” Mitosis or Meiosis

11. PROKARYOTIC CELL DIVISION • Bacterial genes are carried on a single bacterial chromosome (chromosome is a loosely defined term). • Shape = naked (no protein) circular/ single loop- not paired strands as in eukaryotes. • The origin of replication is the first replicated region of the DNA chromosomes. Copies move apart rapidly to opposite poles of the cell. • Prokaryotes undergo binary fission = “division in half”.

12. Eukaryotic Chromosomes

13. How are eukaryotic chromosomes different from prokaryotic chromosomes? • A Nucleus surrounds the EUK chromosomes • A paired number of DNA molecules- instead of one. Characteristic # of chromosomes per species. Ex. Human 46, Dog 78, Amoeba 12, Cat 38, Chimp 48 3. Overall length of DNA- enormous compared to prokaryotes. (human DNA spans 3 meters) 4. DNA is packaged/condensed into chromatin (DNA + PROTEIN) then into nucleosomes then chromosomes. (methylation)

14. a single chromosome is a long, linear DNA molecule, containing hundreds or thousands of genes. chromatin is the DNA-histone protein complex. chromosomes assume the compact shape prior to cell division.

15. Homologous Pairs of Chromosomes • Homologous = same • Chromosome pairs of the same length containing the same genes. • One is inherited from the organism’s father- the other from the organism’s mother during fertilization. • Good = back up copy of each gene in case one is mutated and nonfuntional.

16. REPLICATED DNA • CHROMATIDS are connected, identical copies of the chromosome’s DNA molecule • the CENTROMERE is the narrow “waist” of the duplicated chromosome. • portion of the chromatids that is “moved” during cell division.

17. DIVISION OF THE CHROMOSOMES WITHIN THE NUCLEUS Mitosis = unicellular eukaryotes & multicell somatic cells Mitosis passes a complete genome from the parent cell to daughter cells. makes identical diploid (chromosome pairs) cells Ex. more muscle cells, more skin cells, more nerve cells Meiosis = Germ cell division Meiosis, a reduction division, followed by fertilization ensures genetic diversity in sexually reproducing organisms. makes haploid (single chromosomes) sex cells Ex. sperm or eggs

18. What is the difference between mitosis/meiosis and cytokinesis? • Mitosis/Meiosis is nuclear division- refers to the separation of replicated chromosomes (DNA). • Cytokinesis is division of the cytoplasm once 2 new nuclei have been established.

19. What is the cell cycle? INTERPHASE- 3 phases • THE Cell • Grows • copies its DNA (synthesis) • prepares for nuclear division (mitosis) . • G1,S,G2 • 90% of the cycle MITOSIS/MEIOSIS nuclear division- chromosome movement via spindle fibers CYTOKINESIS cytoplasmic division

20. The cell cycle is directed by internal controls or checkpoints. Internal and external signals provide stop-and-go signs at the checkpoints. Nondividing cells may exit the cell Cycle (G0); or hold at a particular stage in the cell cycle. The most important checkpoint is G1. A “stop” signal causes the cell to enter into a stage where it no longer divides(G0). Instead, it specializes and carries out the programmed functions of that kind of cell. Ex. manufacture protein or contract Cells in (G0) can reenter the cell cycle when given appropriate cues. Ex. tissue damage or hormone signal Three “checkpoints”

21. Regulation of the Cell CycleINTERNAL CONTROL by a distinct cell cycle control system Which chemicals control the cell cycle? • Protein kinases- enzymes that activate or inactivate proteins by phosphorylating them. • Cyclin- Cyclins are proteins that fluctuate in concentration in the cell- giving them their name. Activates a kinase by attaching to it. • Cyclin-dependent Kinases (Cdks) are inactive until cyclin binds to them.

22. MPF was the first cdk + cyclin complex discovered “maturation-promoting factor” Or “M-Phase-Promoting factor” Gets the cell past the G2 checkpoint So it is followed by nuclear division. There are more examples of these protein complexes that bind cyclin to get the cell past all the regulatory checkpoints. Checkpoints: G1, G2, and M

23. Figure 12.12 Evidence for cytoplasmic chemical signals in cell cycle regulation

24. Regulation of the Cell CycleEXTERNAL CONTROL by a distinct cell cycle control system The effect of a growth factor on cell division • Growth factor- protein released by certain body cells that stimulates other cells to divide. Ex. PDGF (platelet derived growth factor) 2. Anchorage dependence- cells must be attached to a substratum like the extra cellular matrix of tissue. 3. Density-dependent inhibition- crowded cells stop dividing.

25. What happens when cells produce an excess amount of cyclin?

26. Cancer • What is cancer? Unregulated cell growth and division. • What causes cancer? Damage to the genes regulating the cell division cycle. • Usually by carcinogens. • Cancer results from disruptions in cell cycle control Winter break reading: “The Immortal Life of Henrietta Lacks” By Rebecca Skloot

27. Tumor = a cluster of cancerous cells • Metastases = When cells leave the tumor, spread, grow new tumors. • Sarcomas = Tumors of the cells in connective tissue, muscle or bone. • Carcinoma = Tumors of cells in epithelial tissue like skin. • The three deadliest human cancers: 1. Lung …smoking 2. Colorectal …diet 3. Breast…causes is still unknown, however some forms are inherited as the genes BRCA1 and BRCA 2.

28. Figure 12-17x2 Mammogram: normal (left) and cancerous (right)

29. Genes that cause cancer are called oncogenes. • The normal versions of these genes are called proto-oncogenes and they code for proteins that stimulate normal cell growth and division. • How do proto-oncogenes become oncogenes? • Translocation, or movement of fragments of chromosomes (break off and attach somewhere else) that result in being around an active promoter. • Amplification, or increasing the number of copies of the gene in the cell. • Point mutations, change the sequence, creating mutant proteins & VIRUSES!!!

30. Two genes that are significant: ras gene and the p53 gene. • The ras gene creates a protein that influences the cell cycle. • The mutated ras protein is hyperactive, leading to excessive cell division. • The p53 gene becomes active when DNA is damaged and creates a tumor suppressing protein. • Mutating the p53 gene can lead to the formation of tumors. • Chemicals in cigarette smoke induce p53 mutations.

31. 15% of the cancers worldwide are associated with viral infections. • Ex. Human Papilloma Virus & Cervical Cancer • Certain viruses can insert oncogenes others may insert DNA into proto-oncogenes, turning them into oncogenes.

32. Figure 12.0 Mitosis Cell division via mitosis involves the:1. replication, 2. alignment, & 3. separation of chromosomes.

33. Mitosis- replication, alignment, separation of chromosomes

34. Interpase Prophase Metaphase Anaphase Telophase I Perceive Many Anxious Teenagers “IPMAT” The names of the stages of mitosis are the same for meiosis… Memorize them now…

35. Figure 12.5 The stages of mitotic cell division in an animal cell: G2 phase; prophase; prometaphase

36. Figure 12.5 The stages of mitotic cell division in an animal cell: metaphase; anaphase; telophase and cytokinesis.

37. Figure 12.5x Mitosis

38. Figure 12.9 Mitosis in a plant cell

39. INTERPHASE • G1 phase “first gap” • growth by production of proteins and cytoplasmic organelles. • S phase “synthesis” • DNA is replicated • G2 phase “second gap” • cell growth by production of proteins & organelles.

40. PROPHASE • Nucleus & cytoplasmic changes • Chromatin fibers condense into chromosomes • visible “sister chromatids” connected at centromere. • Nucleoli dissapear. • Nuclear envelope breaks down • Centrosomes/ centrioles migrate to opposite poles

41. METAPHASE • Centrosomes are at opposite poles • Chromosomes line up in the “middle” at the metaphase plate • Kinetochores (from centromere) attached to microtubules=spindle fibers (from centrosomes) • Whole thing called the “mitotic spindle”

42. Figure 12.6 The mitotic spindle at metaphase

43. ANAPHASE • paired centromeres separate= • Sister chromatids separate • Each now = chromosome • Kinetochore microtubules shorten @ end • Each pole has equivalent and complete collections of chromosomes

44. Figure 12.7 Testing a hypothesis for chromosome migration during anaphase

45. TELOPHASE • Non-kinetochore microtubules elongate the cell • Daughter nuclei form • Chromosomes become less tightly coiled into chromatin.

46. CYTOKINESIS • Division of the cytoplasm • Cleavage furrow (animals) pinches the cell in two. • Cell plate (plants) formed as vesicles deposit cell wall materials to the middle of the cell.

47. Figure 12.8 Cytokinesis in animal and plant cells

48. Figure 12-09x Mitosis in an onion root

49. When does mitosis occur? (after DNA replication.) 2. What is the product of Mitosis followed by cytokinesis? (two genetically identical daughter cells.) 3. Mitosis plays a role in what three activities of life? (growth, repair, and asexual reproduction) 4. Mitosis is a continuous process with observable structural features along the mitotic process. What is the order of the processes? (replication, alignment, separation).

50. The end.