Mitosis Notes

1.         General

            a.         Cell division is called mitosis. For single celled organisms, mitosis increases the number of individuals; for multi-celled organisms, mitosis adds to growth, differentiation and repair.

            b.         Mitosis has two basic function

                        i.         Duplicate the cell

                        ii.        Ensure that each daughter cell has a complete copy of the DNA

            c.         The basic steps are

                        i.         Duplicate the DNA

                        ii.        Divide the chromosomes into two complete sets

                        iii.       Divide the cell into two daughter cells

            d.         Bacteria reproduce by binary fission. The bacterial chromosome is duplicated and the cell splits in half.

2.         Organization of the eukaryote genome

            a.         The complete collection of hereditary material for a cell is called the genome. The genome is organized into one or more very long pieces of DNA called chromosomes.

            b.         Arranged along the chromosomes are shorter sections of DNA called genes which each code for a particular protein.

            c.         Each species has a characteristic number of chromosomes. For humans, this number is 46 for somatic cells - i.e., all cells except reproductive cells, or gametes. The latter have only 23 chromosomes.

            d.         DNA is associated with a variety of proteins which maintain the structure of the chromosome and help control the expression of genes. The DNA-protein combination is called chromatin.

            e.         During mitosis, the sister chromatids are pulled apart, one toward each end of the cell. The cytoplasm is then divided in a process called cytokinesis.

3.         Cell cycle

            a.         The cell cycle (Fig. 11.5) consists of mitosis (10%) and interphase (90%).

                        i.         Interphase

                                    (1)       Interphase includes all cell activity between mitotic divisions.

                                    (2)       It consists of 3 subphases - G₁, S, and G₂. During these subphases the cell grows by synthesizing proteins and cytoplasmic organelles, including the centrioles. During S phase, the chromosomes are duplicated.

                                    (3)       Cells must synthesize enough cytoplasm for the two daughter cells.

                        ii.        Mitotic (M) Phase (Fig. 11.6)

                                    (1)       Prophase

                                                (a)       The chromosomes shorten and thicken.

                                                (b)       Centrioles move to opposite poles of the cell.

                                                (c)       Spindle fibers, made of microtubules, are constructed to extend from the centrioles toward each pair of sister chromatids. The spindle apparatus consists of kinetochore and nonkinetochore microtubules.

                                                (d)       Each chromosome is duplicated and the copies remain attached together and are called sister chromatids. They remain attached to one another at a region of the chromosome called the centromere.

                                                (e)       The nuclear membrane dissolves.

                                                (f)        After the nuclear membrane dissolves, the spindle fibers can attach to the sister chromatids. Special structures at the centromere region called kinetochores provide a place of attachment for kinetochore microtubules. Nonkinetochore microtubules overlap those from the opposite pole.

                                    (2)       Metaphase

                                                (a)       During late prophase chromatids begin to move toward the cell equator (metaphase plate).

                                                (b)       At metaphase the chromatids are aligned at the equator.

                                                (c)       The kinetochores of sister chromatids face opposite poles so that each sister chromatid is attached to kinetochore microtubules from opposite ends of the cell.

                                    (3)       Anaphase

                                                (a)       Chromatids begin to move apart, toward opposite poles.

                                                (b)       Once separated, the chromatids are again called chromosomes.

                                                (c)       By the sliding past one another of nonkinetochore microtubules, the cell elongates.

                                    (4)       Telophase

                                                (a)       Nonkinetochore microtubules elongate the cell further.

                                                (b)       The chromosomes reach opposite poles of the cell and become less tightly coiled.

                                                (c)       Spindle fibers dissolve.

                                                (d)       Nuclear membrane reforms at each end of the cell.

                                                (e)       Cytokinesis has begun.

                        iii.       Cytokinesis

                                    (1)       The division of cytoplasm after separation of the chromosomes

                                    (2)       In animal cells the cleavage furrow forms as the cell membrane is pinched inward to divide the cell into two daughter cells. (Fig. 11.9 a). A ring of microfilaments on the cell membrane contracts, pinching the cell in two. The result is two, separate cells.

                                    (3)       In plant cells, the cell wall precludes the formation of a cleavage furrow. Instead, during telophase, a cell plate forms across the elongating cell where the metaphase plate was. The result is two new daughter cells that are connected together by the shared wall between them. (Fig. 11.9 b)

4.         Control of cell division

            a.         For an organism to develop normally, cell division must be controlled and coordinated.

            b.         Growth factors - Most cells will only divide if molecules called growth factors are present.

            c.         Cell density - When cells become crowded, they normally stop dividing. Most cells also require that they be attached to some substrate in order to divide.

            d.         Cell size - The cell must grow to a certain size in G₁ before it proceeds to S phase. It somehow checks the ratio of cell volume to the amount of DNA in the nucleus. As a cell grows, it’s volume increases but the amount of DNA remains constant. At some point, the ratio becomes such that the cell proceeds to S phase. What would happen if this check were not in place?

            e.         Restriction point - Just before S phase, the cell checks to be sure that all internal and external cues are favorable for division. If everything is good, the cell proceeds to S phase. If not, the cell may exit the cell cycle and enter the nondividing G₀ phase. Most cells are actually in G₀ and will not divide again, while others can reenter the cycle.

            f.         Regulatory proteins (Fig. 11.13)

                        i.         Enzymes called protein kinases, catalyze the phosphorylation of other proteins. This usually activates the phosphorylated protein. The activated protein can then perform some task that moves the cell to the next event in the cell cycle.

                        ii.        The activity of these protein kinases is controlled by the concentration of other proteins called cyclins. Many kinases are only active when attached to a particular cyclin. For this reason the kinases are called cyclin-dependant kinases, or Cdk. his way, a particular Cdk can be present at constant concentration but it’s activity can vary depending on the [cyclin] in the cell.

5.         Cancer

            a.         Cancer is uncontrolled, rapid cell division

            b.         Normal cells grow, divide and stop dividing in response to signals from other cells.

            c.         Cancer cells grow faster and ignore these signals.

            d.         Normal cells tend to stick to similar cells and stop dividing when they lose their attachment. Cancer cells do not, but tend to break away and settle in other parts of the body, a process called metastasis.

            e.         Cancer cells do not maintain their function but behave as unspecialized cells. They consume large amounts of resources to grow and divide but do not contribute to the functioning of the organism.

            f.         The disease is believed to arise from changes in genes which normally help to control cell growth and division. Often, segments of DNA are transposed from one location to another in the genome. Also, many mutagens are known to cause cancer. This suggests that changes to DNA can cause cancer.

            g.         Certain genes turn on cell division but are silent in their normal location. If they get transposed to another location they become active and cause cells to continue dividing. This can lead to cancer. These genes are called oncogenes.

            h.         Most cells die after 20-50 cell divisions but cancer cells are believed to be immortal. E.g., a line of cancer cells called HeLa cells have been dividing in vitro since 1951.