The document summarizes key aspects of the cell cycle and cell division. It describes how cell division results in genetically identical daughter cells through DNA replication and separation of chromosomes. The major phases of the cell cycle are interphase and the mitotic phase. Interphase includes the G1, S, and G2 phases where the cell grows and duplicates its DNA. The mitotic phase includes mitosis and cytokinesis to split the cell into two. Cell division is tightly regulated by cyclins and CDKs to ensure proper progression and duplication of genetic material.

1. Chapter 12 The Cell Cycle

2. Overview: The Key Roles of Cell Division The continuity of life Is based upon the reproduction of cells, or cell division. Figure 12.1

3. Unicellular organisms reproduce by cell division. 100 µm (a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual organism (LM). Figure 12.2 A

4. Multicellular organisms depend on cell division for: Development from a fertilized cell. Growth. Repair. 20 µm 200 µm (b) Growth and development. This micrograph shows a sand dollar embryo shortly after the fertilized egg divided, forming two cells (LM). (c) Tissue renewal. These dividing bone marrow cells (arrow) will give rise to new blood cells (LM). Figure 12.2 B, C

5. The cell division process is an integral part of the cell cycle.

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 .

7. Cellular Organization of the Genetic Material A cell’s endowment of DNA, its genetic information is called its genome .

8. The DNA molecules in a cell are packaged into chromosomes . 50 µm Figure 12.3

9. Eukaryotic chromosomes consist of chromatin , a complex of DNA and protein that condenses during cell division. In animals: Somatic cells have two sets of chromosomes Gametes have one set of chromosomes

10. Distribution of Chromosomes During Cell Division In preparation for cell division DNA is replicated and the chromosomes condense.

11. Each duplicated chromosome has two sister chromatids , which separate during cell division. 0.5 µm Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Sister chromatids Centromeres Sister chromatids A eukaryotic cell has multiple chromosomes, one of which is represented here. Before duplication, each chromosome has a single DNA molecule. Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid contains a copy of the DNA molecule. Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells. Figure 12.4

12. Eukaryotic cell division consists of Mitosis , the division of the nucleus. Cytokinesis , the division of the cytoplasm. In meiosis Sex cells are produced after a reduction in chromosome number. This reduction is accomplished by a second division.

13. The mitotic phase alternates with interphase in the cell cycle. A labeled probe can reveal patterns of gene expression in different kinds of cells.

14. Phases of the Cell Cycle The cell cycle consists of The mitotic phase Interphase INTERPHASE G 1 S (DNA synthesis) G 2 Cytokinesis Mitosis MITOTIC (M) PHASE Figure 12.5

15. Interphase can be divided into subphases G 1 phase S phase G 2 phase

16. The mitotic phase is made up of mitosis and cytokinesis. Mitosis has either 4 or 5 phases.

17. 4 or 5 Phases??? 4 Phases: Prophase Metaphase Anaphase Telophase 5 Phases: Prophase Prometaphase Metaphase Anaphase Telophase

18. CELL DIVISION (In Humans) - 4 Phases: Prophase : 1. The nuclear membrane disappears. 2. The centrioles (only in animals) move to the opposite ends/poles of the cell. 3. Spindle Fibers begin to form. The genetic material recoils into the chromosome state (92 chromatids).

19. CELL DIVISION (In Humans) - 4 Phases: Metaphase: 1. The chromosomes line up at the “equator” of the nucleus 2. Spindle fibers coming from the centrioles attach to the chromosomes at the centromeres. The genetic material is in the chromosome state (92 chromatids).

20. CELL DIVISION (In Humans) - 4 Phases: Anaphase: 1. The chromatids are pulled apart by the spindle fibers. 46 chromatids going toward each end of the cell (two ends = 92 chromatids). 2. Cytokinesis begins.

21. CELL DIVISION (In Humans) - 4 Phases: Telophase: “Opposite of prophase.” 1. Two nuclear membranes reappear 2. The centrioles get out of the way 3. Cytokinesis finishes. There are now two identical daughter cells entering G1 Phase, each with 46 chromatids which will quickly turn into a chromatin state and double during the S phase of interphase to give each body cell 23 pairs or 46 individual chromosomes.

22. CELL DIVISION (In Humans):

23. 5 Phases G 2 OF INTERPHASE PROPHASE PROMETAPHASE Centrosomes (with centriole pairs) Chromatin (duplicated) Early mitotic spindle Aster Centromere Fragments of nuclear envelope Kinetochore Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore microtubule Figure 12.6 Nonkinetochore microtubules

24. 5 Phases Centrosome at one spindle pole Daughter chromosomes METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS Spindle Metaphase plate Nucleolus forming Cleavage furrow Nuclear envelope forming Figure 12.6

25. The Mitotic Spindle: A Closer Look The mitotic spindle Is an apparatus of microtubules that controls chromosome movement during mitosis.

26. The spindle arises from the centrosomes and includes spindle microtubules and asters.

27. Some spindle microtubules Attach to the kinetochores of chromosomes and move the chromosomes to the metaphase plate Centrosome Aster Sister chromatids Metaphase Plate Kinetochores Overlapping nonkinetochore microtubules Kinetochores microtubules Centrosome Chromosomes Microtubules 0.5 µm 1 µm Figure 12.7

28. In anaphase, sister chromatids separate a nd move along the kinetochore microtubules toward opposite ends of the cell. EXPERIMENT 1 The microtubules of a cell in early anaphase were labeled with a fluorescent dye that glows in the microscope (yellow). Spindle pole Kinetochore Figure 12.8

29. Nonkinetechore microtubules from opposite poles overlap and push against each other, elongating the cell. In telophase genetically identical daughter nuclei form at opposite ends of the cell.

30. Cytokinesis: A Closer Look In animal cells Cytokinesis occurs by a process known as cleavage, forming a cleavage furrow . Cleavage furrow Contractile ring of microfilaments Daughter cells 100 µm (a) Cleavage of an animal cell (SEM) Figure 12.9 A

31. In plant cells, during cytokinesis A cell plate forms. Daughter cells 1 µm Vesicles forming cell plate Wall of patent cell Cell plate New cell wall (b) Cell plate formation in a plant cell (SEM) Figure 12.9 B

32. Mitosis in a plant cell 1 Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from. Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelop will fragment. Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate. Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of cell as their kinetochore microtubles shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell. 2 3 4 5 Nucleus Nucleolus Chromosome Chromatin condensing Figure 12.10

33. Binary Fission Prokaryotes (bacteria) reproduce by a type of cell division called binary fission .

34. Binary Fission The bacterial chromosome replicates. The two daughter chromosomes actively move apart. Figure 12.11 Origin of replication E. coli cell Bacterial Chromosome Cell wall Plasma Membrane Two copies of origin Origin Origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. 1 Replication continues. One copy of the origin is now at each end of the cell. 2 Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. 3 Two daughter cells result. 4

35. The Evolution of Mitosis Since prokaryotes preceded eukaryotes by billions of years it is likely that mitosis evolved from bacterial cell division. Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis carried out by most eukaryotic cells.

36. A hypothetical sequence for the evolution of mitosis Figure 12.12 A-D Most eukaryotes. In most other eukaryotes, including plants and animals, the spindle forms outside the nucleus, and the nuclear envelope breaks down during mitosis. Microtubules separate the chromosomes, and the nuclear envelope then re-forms. Dinoflagellates. In unicellular protists called dinoflagellates, the nuclear envelope remains intact during cell division, and the chromosomes attach to the nuclear envelope. Microtubules pass through the nucleus inside cytoplasmic tunnels, reinforcing the spatial orientation of the nucleus, which then divides in a fission process reminiscent of bacterial division. Diatoms. In another group of unicellular protists, the diatoms, the nuclear envelope also remains intact during cell division. But in these organisms, the microtubules form a spindle within the nucleus. Microtubules separate the chromosomes, and the nucleus splits into two daughter nuclei. Prokaryotes. During binary fission, the origins of the daughter chromosomes move to opposite ends of the cell. The mechanism is not fully understood, but proteins may anchor the daughter chromosomes to specific sites on the plasma membrane. (a) (b) (c) (d) Bacterial chromosome Microtubules Intact nuclear envelope Chromosomes Kinetochore microtubules Intact nuclear envelope Kinetochore microtubules Fragments of nuclear envelope Centrosome

37. The cell cycle is regulated by a molecular control system: The frequency of cell division varies with the type of cell. These cell cycle differences result from regulation at the molecular level.

38. Evidence for Cytoplasmic Signals Molecules present in the cytoplasm r egulate progress through the cell cycle. In each experiment, cultured mammalian cells at two different phases of the cell cycle were induced to fuse. When a cell in the M phase was fused with a cell in G 1 , the G 1 cell immediately began mitosis— a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. EXPERIMENTS RESULTS CONCLUSION The results of fusing cells at two different phases of the cell cycle suggest that molecules present in the cytoplasm of cells in the S or M phase control the progression of phases. When a cell in the S phase was fused with a cell in G 1 , the G 1 cell immediately entered the S phase—DNA was synthesized. S S S M M M G 1 G 1 Experiment 1 Experiment 2 Figure 12.13 A, B

39. The Cell Cycle Control System The sequential events of the cell cycle aAre directed by a distinct cell cycle control system, which is similar to a clock. Figure 12.14 Control system G 2 checkpoint M checkpoint G 1 checkpoint G 1 S G 2 M

40. The clock has specific checkpoints w here the cell cycle stops until a go-ahead signal is received. G 1 checkpoint G 1 G 1 G 0 (a) If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. (b) If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0 , a nondividing state. Figure 12.15 A, B

41. 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).

42. The activity of cyclins and Cdks f luctuates during the cell cycle. During G 1 , conditions in the cell favor degradation of cyclin, and the Cdk component of MPF is recycled. 5 During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G 1 phase. 4 Accumulated cyclin molecules combine with recycled Cdk mol- ecules, producing enough molecules of MPF to pass the G 2 checkpoint and initiate the events of mitosis. 2 Synthesis of cyclin begins in late S phase and continues through G 2 . Because cyclin is protected from degradation during this stage, it accumulates. 1 Cdk Cdk G 2 checkpoint Cyclin MPF Cyclin is degraded Degraded Cyclin G 1 G 2 S M G 1 G 1 S G 2 G 2 S M M MPF activity Cyclin Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle (b) Molecular mechanisms that help regulate the cell cycle MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase. 3 Figure 12.16 A, B M

43. Stop and Go Signs: Internal and External Signals at the Checkpoints Both internal and external signals control the cell cycle checkpoints.

44. Growth factors s timulate other cells to divide. EXPERIMENT A sample of connective tissue was cut up into small pieces. Enzymes were used to digest the extracellular matrix, resulting in a suspension of free fibroblast cells. Cells were transferred to sterile culture vessels containing a basic growth medium consisting of glucose, amino acids, salts, and antibiotics (as a precaution against bacterial growth). PDGF was added to half the vessels. The culture vessels were incubated at 37°C. 3 2 1 Petri plate Without PDGF With PDGF Scalpels Figure 12.17

45. In density-dependent inhibition c rowded cells stop dividing. Most animal cells exhibit anchorage dependence i n which they must be attached to a substratum to divide. 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). Normal mammalian cells. The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer. (a) 25 µm Figure 12.18 A

46. Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence. 25 µm Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. Cancer cells. Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells. (b) Figure 12.18 B

47. Loss of Cell Cycle Controls in Cancer Cells Cancer cells do not respond normally to the body’s control mechanisms. Therefore they form masses of cells called tumors .

48. Malignant tumors invade surrounding tissues and can metastasize , exporting cancer cells to other parts of the body where they may form secondary tumors. Figure 12.19 Cancer cells invade neighboring tissue. 2 A small percentage of cancer cells may survive and establish a new tumor in another part of the body. 4 Cancer cells spread through lymph and blood vessels to other parts of the body. 3 A tumor grows from a single cancer cell. 1 Tumor Glandular tissue Cancer cell Blood vessel Lymph vessel Metastatic Tumor

49. The Immortal Cells of Henrietta Lacks This new species is Helacyton gartleri; it is the cell line cultured from the diseased cervix of Henrietta Lacks. The culture was created by George and Margaret Gey in 1951. They were researchers who were sent a sample of Henrietta Lack’s’ tumor. They had wanted to understand cancer, but were frustrated by, among other things, by the inability to maintain a culture of human cells in the laboratory. Inevitably, cells taken for culture would weaken and die. They had been trying for 20 years grow human cells in vitro without success. Until Henrietta Lacks. Her cells were found to be amazingly viable, and the Hela cell line was underway. A little too underway, as it turned out as she died a mere 9 months later from cancer that had spread throughout her body Modern DNA techniques can distinguish Hela cells from other cell lines, and they can also show that Henrietta Lacks cancer was initially cervical cancer, probably the result of human papilloma virus infection. The cells were cultured without her knowledge or consent, and her family remained ignorant of her role until 1975. Henrietta Lacks's contribution to science is now more openly acknowledged, but still little known.