1. Reproduction of Cells and the Cell Cycle Chapter 12

2. Functions of Cell Division (mitosis) Multicellular organisms: growth, development, and repair. Multicellular organisms: growth, development, and repair. Cell division allows organisms to grow while maintaining surface area-to-volume ratio; adds more cells. Cell division allows organisms to grow while maintaining surface area-to-volume ratio; adds more cells. Also provides more cells that can become specialized, as well as replacing damaged or dead cells. Also provides more cells that can become specialized, as well as replacing damaged or dead cells. Unicellular organisms: reproduction. Unicellular organisms: reproduction. Cell division, also called binary fission, is a form of asexual reproduction. Cell division, also called binary fission, is a form of asexual reproduction. New cells will be clones of the original cell. New cells will be clones of the original cell.

4. Chromosomes Eukaryotic cells contain genes (sequences of DNA) which are organized into multiple chromosomes. Eukaryotic cells contain genes (sequences of DNA) which are organized into multiple chromosomes. Chromosomes -- Threadlike structures composed of DNA and proteins. Chromosomes -- Threadlike structures composed of DNA and proteins. Each species has a characteristic chromosome number; Human somatic (body) cells have 46; diploid number. Each species has a characteristic chromosome number; Human somatic (body) cells have 46; diploid number. Gametes (sperm and egg) contain half the number of chromosomes of somatic cells; Human gametes have 23; haploid number. Gametes (sperm and egg) contain half the number of chromosomes of somatic cells; Human gametes have 23; haploid number. Chromatin -- a long, thin fiber that is folded and coiled to form the chromosome. Chromatin -- a long, thin fiber that is folded and coiled to form the chromosome.

5. Chromosomes (cont) Before division, chromosomes are duplicated, forming an X-shaped structure made up of two identical strands of DNA (sister chromatids) joined at a specialized region called the centromere or kinetochore. Before division, chromosomes are duplicated, forming an X-shaped structure made up of two identical strands of DNA (sister chromatids) joined at a specialized region called the centromere or kinetochore.

7. The Cell Cycle Cell cycle -- Sequence of events including mitosis, cytokinesis, cell growth, and preparation for the next division. Cell cycle -- Sequence of events including mitosis, cytokinesis, cell growth, and preparation for the next division. Some cells divide each hour, others take more than 24 hours; Nerve and muscle cells never or rarely divide once they are formed. Some cells divide each hour, others take more than 24 hours; Nerve and muscle cells never or rarely divide once they are formed. Interphase -- includes most of a cell's growth and metabolic activities; about 90% of the cell cycle. Interphase -- includes most of a cell's growth and metabolic activities; about 90% of the cell cycle. 1. G 1 phase – cell growth. (G stands for "gap".) 1. G 1 phase – cell growth. (G stands for "gap".) 2. S phase -- DNA is made as chromosomes are duplicated. (S stands for "synthesis".) 2. S phase -- DNA is made as chromosomes are duplicated. (S stands for "synthesis".) 3. G 2 phase – final prep for division and cell growth. 3. G 2 phase – final prep for division and cell growth.

8. Cell Cycle Cont. M phase -- shortest part of the cell cycle; cell divides. M phase -- shortest part of the cell cycle; cell divides. 1. Mitosis -- division of the nucleus. 1. Mitosis -- division of the nucleus. Five stages: prophase, prometaphase, metaphase, anaphase and telophase. Five stages: prophase, prometaphase, metaphase, anaphase and telophase. 2. Cytokinesis -- division of the cytoplasm (cytosol and organelles). 2. Cytokinesis -- division of the cytoplasm (cytosol and organelles).

10. Processes of Cell Division 1. Replication: 1. Replication: By late interphase, chromosomes have been duplicated and take the form of loosely packed chromatin. By late interphase, chromosomes have been duplicated and take the form of loosely packed chromatin. 2. Alignment: 2. Alignment: Prophase, prometaphase, and metaphase. Prophase, prometaphase, and metaphase. Nuclear membrane breaks down, chromatin fibers condense into observable chromosomes. Nuclear membrane breaks down, chromatin fibers condense into observable chromosomes. Spindle forms, composed of microtubules. Spindle forms, composed of microtubules.

11. Processes of Cell Division cont. 2. Alignment continues: 2. Alignment continues: Spindle fibers (bundles of microtubules) extend from each pole toward the cell's equator; some attach to chromosomes. Spindle fibers (bundles of microtubules) extend from each pole toward the cell's equator; some attach to chromosomes. Chromosomes move to the metaphase plate, the plane between the poles. Chromosomes move to the metaphase plate, the plane between the poles. Centromeres of all chromosomes are aligned on the metaphase plate, connected to spindle fibers. Centromeres of all chromosomes are aligned on the metaphase plate, connected to spindle fibers.

13. Processes of Cell Division cont. 3. Separation: 3. Separation: Anaphase, telophase, and cytokinesis Anaphase, telophase, and cytokinesis Centromeres divide as sister chromatids pull apart into separate chromosomes and move towards opposite poles of the cell. Centromeres divide as sister chromatids pull apart into separate chromosomes and move towards opposite poles of the cell. Microtubules shorten as chromosomes approach the poles. Microtubules shorten as chromosomes approach the poles. The poles of the cell also move farther apart, elongating the cell. The poles of the cell also move farther apart, elongating the cell.

14. Processes of Cell Division (end) 3. Separation continues: 3. Separation continues: Daughter nuclei begin to form at the two poles. Daughter nuclei begin to form at the two poles. Nuclear envelopes form around the chromosomes. Nuclear envelopes form around the chromosomes. Nucleoli reassemble. Nucleoli reassemble. Chromatin of each chromosome uncoils and the chromosomes become less distinct. Chromatin of each chromosome uncoils and the chromosomes become less distinct. Cytokinesis begins with cleavage (animal cells) or cell plate formation (plant cells). Cytokinesis begins with cleavage (animal cells) or cell plate formation (plant cells). In plants, a new cell wall forms as cellulose is deposited between the two membranes of the cell plate. In plants, a new cell wall forms as cellulose is deposited between the two membranes of the cell plate.

18. Cell Cycle Animation Cell Cycle Animation

19. Regulation of the Cell Cycle External and internal cues control cell division. External and internal cues control cell division. 1. Cell membrane receptors (nutrients, pH, chemical growth factors). 1. Cell membrane receptors (nutrients, pH, chemical growth factors).Cell membrane receptors Cell membrane receptors PDGF (platelet derived growth factor) is made by blood platelets; binds to membrane receptors (tyrosine kinases) and causes cells to divide to heal wounds. PDGF (platelet derived growth factor) is made by blood platelets; binds to membrane receptors (tyrosine kinases) and causes cells to divide to heal wounds. 2. Cell density -- Crowding inhibits cell division (density-dependent inhibition). 2. Cell density -- Crowding inhibits cell division (density-dependent inhibition).

20. Regulation of the Cell Cycle cont. 3. G 1 phase of the cell cycle -- If a cell is going to divide, it progresses beyond the R (restriction) point then proceeds with DNA synthesis. Checkpoints 3. G 1 phase of the cell cycle -- If a cell is going to divide, it progresses beyond the R (restriction) point then proceeds with DNA synthesis. CheckpointsCheckpoints –If the cell is not going to divide, it may exit from the cell cycle at the restriction point and switch to a nondividing state called the G 0 phase. 4. Cell size -- cytoplasmic volume is the most important indicator of whether a cell will pass the restriction point. 4. Cell size -- cytoplasmic volume is the most important indicator of whether a cell will pass the restriction point.

21. Regulation of the Cell Cycle (cont) 5. Regulatory proteins – Cyclin and protein kinases. 5. Regulatory proteins – Cyclin and protein kinases. Cyclin is produced and accumulates during interphase, then triggers mitosis. Cyclin is produced and accumulates during interphase, then triggers mitosis. An example of a cyclin-dependent kinase is MPF (maturation promoting factor). An example of a cyclin-dependent kinase is MPF (maturation promoting factor). Active MPF phosphorylates chromatin proteins, causing chromosomes to condense. Active MPF phosphorylates chromatin proteins, causing chromosomes to condense. Nuclear envelope breaks down when some of its membrane proteins are phosphorylated. Nuclear envelope breaks down when some of its membrane proteins are phosphorylated. Near the end of mitosis, cyclin is destroyed by an enzyme that is activated by MPF. Near the end of mitosis, cyclin is destroyed by an enzyme that is activated by MPF. The destruction of cyclin causes the decline in active MPF at the end of mitosis. The destruction of cyclin causes the decline in active MPF at the end of mitosis. (ANOTHER EXAMPLE OF FEEDBACK CONTROL) (ANOTHER EXAMPLE OF FEEDBACK CONTROL) (ANOTHER EXAMPLE OF FEEDBACK CONTROL) (ANOTHER EXAMPLE OF FEEDBACK CONTROL)

22. Cancer cells escape from the controls on cell division Cancer cells divide excessively and ignore density-dependent inhibition. Cancer cells divide excessively and ignore density-dependent inhibition. Cancer cells will divide indefinitely as long as nutrients are available. Normal mammalian cells divide about 20 to 50 times before they stop; there is a culture of cancer cells that have been dividing in a lab since 1951 (HeLa). Cancer cells will divide indefinitely as long as nutrients are available. Normal mammalian cells divide about 20 to 50 times before they stop; there is a culture of cancer cells that have been dividing in a lab since 1951 (HeLa).HeLa The immune system normally destroys abnormal cells that have converted from normal to cancer cells. The immune system normally destroys abnormal cells that have converted from normal to cancer cells. If not destroyed, abnormal cells form a tumor. If not destroyed, abnormal cells form a tumor. In benign tumors, the cells remain at the original site. In benign tumors, the cells remain at the original site. A tumor is malignant (cancer) if the cells have the ability to damage tissue and to spread to other parts of the body. A tumor is malignant (cancer) if the cells have the ability to damage tissue and to spread to other parts of the body. Detached cancer cells may spread into other tissues surrounding the original tumor and may even enter the blood and lymph vessels of the circulatory system (metastasis). Detached cancer cells may spread into other tissues surrounding the original tumor and may even enter the blood and lymph vessels of the circulatory system (metastasis).

24. Tumor Suppressor Genes The protein products of tumor suppressor genes can directly or indirectly prevent cell division or lead to cell death.The protein products of tumor suppressor genes can directly or indirectly prevent cell division or lead to cell death. Tumor suppressors can be likened to the brake system in a car.Tumor suppressors can be likened to the brake system in a car. Loss of function of tumor suppressors leads to abnormal cellular behavior.Loss of function of tumor suppressors leads to abnormal cellular behavior. Car AnalogyCar Analogy Car AnalogyCar Analogy

25. Key Tumor Suppressor Genes P53P53 –A transcription factor that regulates genes controlling cell division and cell death. –Important in the cellular response to DNA damage. –Aids in decision between repair and induction of cell death. BRCABRCA –BRCA proteins have multiple functions including repairing DNA damage and regulation of gene expression. –Non-functional BRCA leads to compromised DNA repair and gene regulation. (Animation) (Animation)

26. Cancer Treatment New cancer drugs target the cell cycle by inhibiting division internally or externally. New cancer drugs target the cell cycle by inhibiting division internally or externally. Taxol and spindle formation Taxol and spindle formation Taxol and spindle formation Taxol and spindle formation Herceptin and membrane receptors animation Herceptin and membrane receptors animation animation