Cell Cycle Notes

1.         Importance of Cell Division

            a.         For single celled organisms, cell division increases the number of individuals.

            b.         In a multicellular organism, cell division functions to repair and renew cells that die from normal wear and tear or accidents.

            c.         Cell division enables a multicellular organism to develop from a single fertilized egg or zygote.

                        i.         Approximately 100 trillion cells in the human body all arose from a single cell by mitosis. E.g., red blood cells are made at the rate of one million per second

            d.         Cell division is part of the cell cycle, the life of a cell from its origin in the division of a parent cell until its own division into two daughter cells.

            e.         Cell division has two basic functions:

                        i.         Duplicate the cell

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

            f.         The basic steps are:

                        i.         Duplicate the DNA and form two identical daughter nuclei (mitosis (Gr. dimitos - two threads))

                                    (1)       Each duplicated chromosome consists of two sister chromatids, which contain identical copies of the chromosome’s DNA.

                                    (2)       The chromatids are initially attached by proteins at a region called the centromere.

                        ii.        Divide the chromosomes into two complete sets

                                    (1)       DNA molecules are packaged into chromosomes. Each single chromosome contains one long, linear DNA molecule carrying hundreds or thousands of genes, the units that specify an organism’s inherited traits.

                                    (2)       Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus.

                                    (3)       Human somatic cells (body cells) have 46 chromosomes, made up of two sets of 23 (one from each parent). Human gametes (sperm or eggs) have one set of 23 chromosomes, half the number in a somatic cell.

                        iii.       Divide the cell into two daughter cells (cytokinesis)

2.         Regulation of the Cell Cycle

            a.         The timing and rates of cell division in different parts of an animal or plant are crucial for normal growth, development, and maintenance.

            b.         The frequency of cell division varies with cell type.

                        i.         Some human cells divide frequently throughout life (skin cells).

                        ii.        Others have the ability to divide, but keep it in reserve (liver cells).

                        iii.       Mature nerve and muscle cells do not appear to divide at all after maturity.

            c.         The cell monitors several signals to determine whether it will divide or not. Some signals originate inside the cell, others outside.

                        i.         For example, cells fail to divide if an essential nutrient is left out of the culture medium.

                        ii.        Particularly important for mammalian cells are growth factors, proteins released by one group of cells that stimulate other cells to divide.

                        iii.       Each cell type probably responds specifically to a certain growth factor or combination of factors.

                        iv.       The effect of an external physical factor on cell division can be seen in density-dependent inhibition of cell division.

                                    (1)       Cultured cells normally divide until they form a single layer on the inner surface of the culture container.

                                    (2)       If a gap is created, the cells will grow to fill the gap.

                                    (3)       At high densities, the amount of growth factors and nutrients is insufficient to allow continued cell growth.

                        v.         Most animal cells also exhibit anchorage dependence for cell division.

                                    (1)       To divide, they must be anchored to a surface, typically the extracellular matrix of a tissue.

3.         The Mitotic Cell Cycle

            a.         Interphase occupies about 90% of the cell cycle.

                        i.         It includes all cell activity between mitotic divisions during which the cell is preparing for division. These activities include growing by producing proteins and cytoplasmic organelles and copying its chromosomes.

                        ii.        Interphase has three subphases: the G₁ phase (“first gap”), the S phase (“synthesis”), and the G₂ phase (“second gap”).

                                    (1)       During all three subphases, the cell grows by producing proteins and cytoplasmic organelles such as mitochondria and endoplasmic reticulum.

                                    (2)       However, chromosomes are duplicated only during the S phase.

            b.         A typical human cell might divide once every 24 hours.

                        i.         Of this time, the M phase would last less than an hour, while the S phase might take 10–12 hours, or half the cycle.

                        ii.        The rest of the time would be divided between the G₁ and G₂ phases.

                        iii.       The G₁ phase varies most in length from cell to cell.

                        iv.       Each chromosome is duplicated and the resulting copies are called sister chromatids. They remain attached to one another at a region called the centromere

            c.         The mitotic (M) phase consists of mitosis and cytokinesis.

            d.         Mitosis is usually broken into five subphases: prophase, prometaphase, metaphase, anaphase, and telophase. (Gr. pro - before; meta - between, beside; ana - backward; telo - far, distant)

                        i.         Prophase

                                    (1)       The chromosomes (which are now sister chromatids joined together) shorten and thicken.

                                    (2)       The mitotic spindle begins to form.

                                    (3)       Centrioles move to opposite poles of the cell

                                    (4)       Spindle fibers are constructed to extend from the centrioles toward each chromosome.

                        ii.        Prometaphase

                                    (1)       The nuclear envelope fragments.

                                    (2)       Spindle fibers interact with the condensed chromosomes.

                        iii.       Metaphase

                                    (1)       The spindle fibers push the sister chromatids until they are all arranged at the metaphase plate, an imaginary line across the middle of the cell.

                                    (2)       At metaphase the chromatids are aligned at this “equator.”

                        iv.       Anaphase

                                    (1)       Centromeres divide and sister chromatids begin to be pulled apart by the spindle fibers.

                                    (2)       Once separated, the chromatids are again called chromosomes and they move toward opposite poles.

                                    (3)       By the end of this phase, the two poles have equivalent collections of chromosomes.

                        v.         Telophase

                                    (1)       Spindle fibers dissolve

                                    (2)       Daughter nuclei begin to reform at each pole.

                                    (3)       The chromosomes become less tightly coiled.

                        vi.       Cytokinesis

                                    (1)       The division of the cytoplasm begins near the end of telophase.

                                    (2)       In plant cells, a new cell wall forms to divide the two daughter cells.

                                    (3)       In animal cells the cleavage furrow forms as the cell membrane is pinched inward to divide the cell into two daughter cells.

4.         Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence.

            a.         Cancer cells divide excessively and invade other tissues because they have escaped the body’s control mechanisms.

                        i.         Cancer cells do not stop dividing when growth factors are depleted.

                        ii.        This is either because a cancer cell manufactures its own growth factors, has an abnormal response to cell signals, or has an abnormal cell cycle control system.

                        iii.       If and when cancer cells stop dividing, they do so at random points, not at the normal checkpoints in the cell cycle.

            b.         Cancer cells may divide indefinitely if they have a continual supply of nutrients. In contrast, nearly all mammalian cells divide 20 to 50 times under culture conditions before they stop, age, and die.

            c.         Normal cells tend to stick to similar cells while cancer cells do not.

                        i.         They tend to break away and are carried by the blood and lymph system to other tissues and start more tumors in an event called metastasis.

                        ii.        If the abnormal cells remain at the originating site, the lump is called a benign tumor. Most do not cause serious problems and can be fully removed by surgery.

                        iii.       In a malignant tumor, the cells become invasive enough to impair the functions of one or more organs.

            d.         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.

            e.         The disease is believed to arise from changes in genes which normally help to control cell growth and division.

                        i.         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.

                        ii.        The abnormal behavior of cancer cells begins when a single cell in a tissue undergoes a transformation that converts it from a normal cell to a cancer cell.

                                    (1)       Normally, the immune system recognizes and destroys transformed cells.

                                    (2)       However, cells that evade destruction proliferate to form a tumor, a mass of abnormal cells.

                                    (3)       Also, many mutagens are known to cause cancer, suggesting that changes to DNA can cause cancer

            f.         Cancer cells may be “immortal.”

                        i.         HeLa cells from a tumor removed from a woman (Henrietta Lacks) in 1951 are still reproducing in culture

            g.         Treatments for metastasizing cancers include high-energy radiation and chemotherapy with toxic drugs.

                        i.         These treatments target actively dividing cells.

                        ii.        Chemotherapeutic drugs interfere with specific steps in the cell cycle.

                        iii.       For example, Taxol prevents depolymerization of the mitotic spindle, preventing cells from proceeding past metaphase.

                        iv.       The side effects of chemotherapy are due to the drug’s effects on normal cells.

5.         Differentiation

            a.         For the first several divisions after fertilization, every cell produced is identical.

                        i.         As the number of cells increases, groups of cells differentiate to form tissues and organs.

                        ii.        Because each cell has the same DNA, they each have all the instructions to produce a complete organism. This is called totipotency.

                        iii.       As they differentiate, most animal cells lose totipotency while most plant cells do not. At birth, most cells are already differentiated and simply grow and divide to adulthood.

            b.         Cell differentiation allows specialization and division of labor. E.g., a skin cell never becomes any other type of cell.

            c.         A cell remains a specific type because of the information it receives from nearby cells and/or the external environment. The signals that trigger cell differentiation are not yet well understood.

            d.         Differentiated cells perform selected tasks for the organism and ensure that a multicellular organism is as efficient as a unicellular one.

6.         Cloning

            a.         Production of genetically identical individuals

                        i.         Fetal cow cells or cells from the ovary are harvested because they are still totipotent.

                        ii.        An electrical jolt triggers cell division.

                        iii.       The growing embryo is then implanted into the uterus of the surrogate mother.

                        iv.       The offspring is genetically identical to the original donor.

            b.         Producing genetically identical organisms which carry a useful gene.

                        i.         Construct a piece of DNA carrying a gene of interest and a gene for antibiotic resistance. Insert this DNA into fetal cells.

                        ii.        Grow the cells on a medium containing the antibiotic so that only the cells with the inserted DNA will survive.

                        iii.       Insert the nuclei from surviving cells into enucleated egg cells.

                        iv.       Implant the egg cells into the surrogate mother

                        v.         Clones are born which all carry the useful gene

            c.         Applications

                        i.         Can produce cows which produce a useful protein in their milk

                        ii.        Produce genetically identical organs for transplantation

                        iii.       Repopulate endangered species

                        iv.       Produce human tissue