CHAPTER 11 THE REPRODUCTION OF CELLS Mitosis Cells divide to make more cells. While all the other organelles can be randomly separated into the daughter cells, the chromosomes must be precisely divided so that each daughter cell gets exactly the same DNA. Mitosis is normal cell division, which goes on throughout life in all parts of the body. Meiosis is the special cell division that creates the sperm and eggs, the gametes. Mitosis and meiosis occur in eukaryotes. Prokaryotes use a different method—”fission” to divide. Humans have 46 chromosomes, 23 from each parent. Every cell has the same 46 chromosomes Each species has a characteristic number of chromosomes: corn ahs 20, house flies have 10, chimpanzees have 48. Chromosomes The essential part of a chromosome is a single very long strand of DNA. This DNA contains all the genetic information for creating and running the organism. The DNA is packaged by proteins bound to it. At different times, these proteins cause the DNA to be spread out like spaghetti in a bowl, or tightly condensed into the X-shaped chromosomes we can see in the microscope. Chromosomes have Chromatids Centromere More Chromosomes Before replication, chromosomes have one chromatid. After replication, chromosomes have 2 sister chromatids, held together at the centromere In mitosis, the two chromatids of each chromosome separate, with each chromatid going into a daughter cell. Remember that diploid cells have two copies of each chromosome, one from each parent. These pairs of chromosomes are NOT attached together. Cell Cycle Some cells divide constantly: (cells in the embryo, skin cells, gut lining cells, etc.) Other cells divide rarely or never: only to replace themselves. Actively dividing cells go through a cycle of events that results in mitosis. Most of the cycle was called “interphase” (the cell increases in size, but the chromosomes are invisible.) The 3 stages: *G1 (“Gap”) is the period between mitosis and S, when each chromosome has 1 chromatid. It is the time when the cell grows and performs its normal function. The *S phase (“Synthesis”) is the time when the DNA is replicated, when the chromosome goes from having one chromatid to having 2 chromatids held together at the centromere. *G2 is the period between S and mitosis. The chromosome have 2 chromatids, and the cell is getting ready to divide. Machinery of Mitosis The chromosomes are pulled apart by the spindle, which is made of microtubules. They attach to each centromere, and anchored on the other end to centrioles. There are 2 centrioles, one at each end of the spindle. The chromosomes are lined up between the poles of the spindle. When they contract, the chromosomes are pulled to the opposing poles. Prophase In prophase, the cell begins the process of division. 1. The chromosomes condense (long & thin to short & fat). 2. The nuclear envelope disappears. 3. The centrioles move to opposite poles. During interphase, the pair of centrioles were together just outside the nucleus. 4. The spindle starts to form, growing out of the centrioles towards the chromosomes. Kinetochore vs Nonkinetochore Kinetochore = protein structure located at centromere regions Kinetochore microtubules = attach to the kinetochores!! (PULL CHROMOSOMES) Nonkinetochore microtubules = overlap with nonkinetochore microtubules from the opposite pole. (ELONGATE CELL) Metaphase chromosomes line up on the equator (metaphase plate) of the cell, with the centrioles at opposite ends and the spindle fibers attached to the centromeres. Entire structure – nonkinetochore microtubules + kinetochore microtubules = spindle Anaphase In anaphase, the centromeres divide. At this point, each chromosome goes from having 2 chromatids to being 2 chromosomes, each with a single chromatid. Then the spindle fibers contract, and the chromosomes are pulled to opposite poles. Telophase Nonkinetochore microtubules elongate the cell The spindle disintegrates The nuclear envelope reforms around the two sets of chromosomes. Daughter nuclei begin to reform The cytoplasm divides into 2 separate cells. Cytoplasmic Division The organelles (other than the chromosomes) get divided up into the 2 daughter cells passively: they go with whichever cell they find themselves in. Plant and animal cells divide the cytoplasm in different ways. In plant cells, a new cell wall made of cellulose forms between the 2 new nuclei, about where the chromosomes lined up in metaphase. Cell membranes form along the surfaces of this wall. When the new wall joins with the existing side wall, the 2 cells have become separate. In animal cells, a ring of actin fibers (microfilaments are composed of actin) forms around the cell equator and contacts, pinching the cell in half. Summary of Mitosis Prophase: • • • • Chromosomes condense Nuclear envelope disappears Centrioles move to opposite sides of the cell Spindle forms and attaches to centromeres on the chromosomes Metaphase • Chromosomes lined up on equator of spindle • Centrioles at opposite ends of cell Anaphase • Centromeres divide: each 2-chromatid chromosome becomes two 1-chromatid chromosomes • Chromosomes pulled to opposite poles by the spindle Telophase • Chromosomes de-condense • Nuclear envelope reappears • Cytoplasm divided into 2 cells PLANT vs ANIMAL PLANT CELL * Cell plate ANIMAL CELL * Cleavage furrow REGULATION OF THE CELL CYCLE GROWTH FACTORS: occur in the presence of a wound – cells respond and grow DENSITY-DEPENDENT INHIBITION: Cells grow depending on the density of cells. (nutrients/space/adhesion) RESTRICTION POINT: go/no go decision. If all systems are “go” (all external and internal conditions are favorable), the step proceeds. G0 phase = nondividing state. Cyclins – concentrations fluctuate cyclically Cdk complex called MPF (maturation promotion factor (M-phase promoting factor) Near end of M-phase, MPF switches off by activating an enzyme that destroys cyclin. 1. cyclin is synthesized through the cycle and accumulates during interphase 2. cyclin attaches to Cdk and the protein complex is activated at the end of interphase 3. MPF coordinates mitosis by phosphorylating varous proteins, including other protein kinases 4. MPF is a cyclin-dependent kinase enzyme that destroys MPF activity. The Cdk component of MPF is recycled, its kinase activity restored by association with new cyclin that accumulates during interphase. Prokaryotic Cells: Binary Fission 1. 2. 3. “Division in half” Most bacterial genes are carried on a single, circular chromosome & associated proteins. Replicates Attaches to different parts of the cell membrane Cell pulls apart and the replicate and original chromosomes are separated. Cancer Cancer is a disease of uncontrolled cell division. It starts with a single cell that loses its control mechanisms due to a genetic mutation. That cell starts dividing without limit, and eventually kills the host. Normal cells are controlled by several factors. They stay in the G1 stage of the cell cycle until they are given a specific signal to enter the S phase, in which the DNA replicates and the cell prepares for division. Cancer cells enter the S phase without waiting for a signal. Another control: normal cells are mortal. This means that they can divide about 50 times and then they lose the ability to die. This “clock” gets re-set during the formation of the gametes. Cancer cells escape this process of mortality: they are immortal and can divide endlessly. A third control: cells that suffer significant chromosome damage destroy themselves due to the action of a gene called “p53”. Cancer cells either lose the p53 gene or ignore its message and fail to kill themselves. Cancer Progression There are many different forms of cancer, affecting different cell types and working in different ways. All start out with mutations in specific genes called “oncogenes”. The normal, unmutated versions of the oncogenes provide the control mechanisms for the cell. The mutations are caused by radiation, certain chemicals (carcinogens), and various random events during DNA replication. Once a single cell starts growing uncontrollably, it forms a tumor, a small mass of cells. No further progress can occur unless the cancerous mass gets its own blood supply. “Angiogenesis” is the process of developing a system of small arteries and veins to supply the tumor. Most tumors don’t reach this stage. A tumor with a blood supply will grow into a large mass. Eventually some of the cancer cells will break loose and move through the blood supply to other parts of the body, where they start to multiply. This process is called metastasis. It occurs because the tumor cells lose the proteins on their surface that hold them to other cells. Cancer Treatment Two basic treatments: surgery to remove the tumor, and radiation or chemicals to kill actively dividing cells. It is hard to remove all the tumor cells. Tumors often lack sharp boundaries for easy removal, and metastatic tumors can be very small and anywhere in the body. Radiation and chemotherapy are aimed at killing actively dividing cells, but killing all dividing cells is lethal: you must make new blood cells, skin cells, etc. So treatment must be carefully balanced to avoid killing the patient. Chemotherapy also has the problem of natural selection within the tumor. If any of the tumor cells are resistant to the chemical, they will survive and multiply. The cancer seems to have disappeared, but it comes back a few years later in a form that is resistant to chemotherapy. Using multiple drugs can decrease the risk of relapse. MITOSIS LAB