1. CH 12 The Cell Cycle

2. Why cell division? 1.Single cell organisms reproduce this way. 2.Multicellular Organisms a.Need this to grow from a fertilized egg (200trillion) b.Need this to repair after grown

3. I.Cell Division Basics A.Organizing Genetic Material 1.Genome: All the genetic info. of a cell. a.After cell division each daughter cell must get the same genome. 2.Chromosomes: A condensed form of DNA found during cell division. a.Humans have 46 chromosomes. (23 from each parent) b.This condensed form of organizes the DNA for division.

4. B. Distributing Chromosomes During Cell Division 1. Chromatin: A complex of DNA and protein 2. In preparation for cell division chromatin coils into chromosomes. a. Each chromosome is made of 2 sister chromatids. (identical) b. Centromere: holds the sisters together.

5. 1.Mitosis: Division of nucleus a.Produces all somatic cells: all body cells (46 chromosomes) b.Not used to make gametes: Reproductive cells (23 chromosomes) 2.Cytokinesis: Division of cytoplasm that follows mitosis.

6. II.Mitosis A.Phases of the cell cycle 1.Interphase (90%): Growth time that has 3 parts a.G1: Cell grows and makes proteins b.S: Cell grows, makes proteins, and copies DNA c.G2: Cell grows and makes proteins INTERPHASE G1G1 S (DNA synthesis) G2G2 Cytokinesis Mitosis MITOTIC (M) PHASE Figure 12.5

7. 2.Mitosis: Dividing the nucleus and evenly distributing the DNA to the daughter cells. a.Prophase: Chromatin fibers begin to tightly coil to make observable chromosomes.tightly coil Spindle begins to form. Made of centrosomes and microtubules Centrosomes start to move away from each other. 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

8. b.Prometaphase: Nuclear envelope fragments Centrosomes reach poles and microtubules reach to chromosomes Kinetochores develop at the centromere of each chromosome 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

9. c.Metaphase: Centrosomes at opposite ends of cell The chromosomes move to the metaphase plate (equator) The kinetochores of each chromatid are attached to a microtubule coming from opposite poles d.Anaphase: Sister chromatids are pulled apart by microtubules Each chromatid travels toward opposite poles Centrosome at one spindle pole Daughter chromosomes METAPHASEANAPHASETELOPHASE AND CYTOKINESIS Spindle Metaphase plate Nucleolus forming Cleavage furrow Nuclear envelope forming Figure 12.6

10. e.Telophase: Two nuclear envelopes start to form around chromosomes at each pole Chromosomes start to uncoil 3.Cytokinesis: Division of the cytoplasm a.Starts during telophase b.Cleavage furrow develops and pinches cell in two. Centrosome at one spindle pole Daughter chromosomes METAPHASEANAPHASETELOPHASE AND CYTOKINESIS Spindle Metaphase plate Nucleolus forming Cleavage furrow Nuclear envelope forming Figure 12.6

11. III.Cell Cycle Control A.The cell cycle is regulated by a molecular system. 1.The regulating molecules are found in the cytoplasm. 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 SSM M MG1G1 G1G1 Experiment 1 Experiment 2 Figure 12.13 A, B

12. B.Cell cycle control System: A set of molecules that trigger events in the cell cycle. 1.Checkpoint: A control point where stop and go signals can regulate the cycle. a.Checkpoints respond to both internal and external controls. b.Most checkpoints stop cell cycle untill overridden by a signal. c.Checkpoints are located at G1, G2, and M phases. Figure 12.14 Control system G 2 checkpoint M checkpoint G 1 checkpoint G1G1 S G2G2 M

13. 2.G 1 The most important checkpoint. a.If G 1 receives a signal, all of cell cycle will continue. b.If G 1 does not receive the signal, the cell will enter G 0 phase, a nondividing state. G 1 checkpoint G1G1 G1G1 G0G0 (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

14. 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 G 2 checkpoint Cyclin MPF Cyclin is degraded Degraded Cyclin G1G1 G2G2 S M G1G1 G1G1 S G2G2 G2G2 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 C.How cycle control works 1.Kinases: Enzymes that activate or inactivate other proteins by phosphorylating them. a.They give the go-ahead at G 1 and G 2 checkpoints. 2.Cyclins: Activate the kinases. 3.The cell produces cyclins to activate the kinases which override the stop points.

15. D.Internal and External Signals: 1.Internal Signals: based on internal happenings. a.Anaphase Signal: kinetichores that are unattached to spindles send a signal that holds sister chromatids together. When all kinetichores are attached to a spindle, the signal stops and sister chromatids are allowed to separate.

16. 2.External Signals: Based on cell surroundings a.Growth Factors: a protein released by one cell that stimulates another cell to divide. Platelet example after an injury. b.Density-Dependent Inhibition: When cells get crowded they stop dividing. c.Anchorage Dependence: Cells won’t divide unless they are attached to something. 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

17. E.Cancer: Loss of cell cycle control 1.Why cancer cells are different a.No density-dependent inhibition b.Don’t need growth factors c.If they stop dividing it is at random places. d.Have the ability to divide forever e.Often secrete signals to tell blood vessels to grow toward the tumor. f.May have abnormal numbers of chromosomes. 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

18. 2.Transformation: The conversion of a normal cell to a cancer cell. a.Usually recognized and killed by the body. b.If not killed will lead to a tumor. 3.Benign Tumor: If cells remain localized to the tumor. 4.Malignant Tumor: If cells start to invade other locations. a.Metastasis: Spread of cancer cells.

19. 5.Treatment of cancer a.Radiation: Used on localized tumors. Damages cancer cells more than normal cells. The cancer cells have lost ability to repair the damage. b.Chemotherapy: Used on metastatic tumors. The drugs interfere with steps of cell cycle. Are harsh b/c they also interfere with normal cells.