Chapter 7 – The Cell Cycle and Cell Division Cells – source of continuity and diversity. The continuity of life depends on the reproduction of cells, called cell division. Cell division is one part of the life cycle of a cell. This life cycle from origin to division is called the cell cycle here’s three reasons why cell division is so important: Unicellular organisms use cell division to make an entire organism (called cloning) Sexually reproducing organisms use cell division to develop from a zygote. In many cases, after an organism is fully grown it uses cell division for renewal and repair. Let’s talk chromosomes!! A cell’s DNA is called its genome. A typical eukaryotic cell has a tremendous amount of DNA A great example of this is a typical human cell which has about 3 meters of DNA…a length about 300,000 times the diameter of the cell itself. Yet all this DNA must be copied, separated and divided evenly between the 2 daughter cells. This task is manageable because the DNA is packaged into chromosomes. Let’s look at a picture of chromosomes in a cell. Every eukaryotic cell has a characteristic number of chromosomes in each cell. Human somatic cells (body cells, not reproductive cells) have 46 chromosomes. The term used to refer to the complete number chromosomes is called diploid number or 2n Human gametes – (sperm and egg) have 23 chromosomes. The term used to refer to half the complete number of chromosomes is called haploid number or n. Chromosomes, chromatin, & chromatids This is a little confusing… Each chromosome is made up of DNA wound around associated proteins. This DNA-protein complex is called chromatin. It condenses after the DNA duplicates in preparation for cell division. Each duplicated chromosome is made up of sister chromatids that are attached at a centromere. Even duplicated and attached, it’s still called a chromosome Sister Chromatids separate during mitosis (division of the cell’s nucleus). One half of each pair travels to one end of the cell with the other half traveling to the other end of the cell. After cytokinesis (division of the cell’s cytoplasm), there are 2 cells that result. Each one has a full complement of the DNA found in cells. Chromosome number We start with your parents, who each have 46 chromosomes in somatic cells. They (your parents) each produced gametes (sperm and egg) with 23 chromosomes in a process called meiosis (production of gametes) The gametes fused to make a zygote (46 chromosomes) (I know, I know…let’s try not to think about that too much!) Mitosis and cytokinesis produced trillions of cells that make up you. Gametes produced by you will one day (many years from now…right???) fuse with another gamete to make a zygote. Both prokaryotes and eukaryotes produces clone cells through a process that includes: Receiving a reproductive signal Replicating the DNA Segregating the DNA cytokinesis Prokaryotes achieve this through binary fission; Eukaryotes achieve this through mitosis Binary fission – best summed up by a diagram on page 128 (Fig. 7.4) Eukaryotes - Cell Cycle Mitosis is just one very small part of the cell cycle. The longest part of the cell cycle (about 90% of the life of a cell) is spent in interphase. Figure 7.8 on page 133 shows the cell cycle with the relative time spend in each stage of cell cycle. Interphase During interphase the cell grow and copies its chromosomes. Interphase can be divided into three subphases: G1 phase (“first gap”) – growth of cell S phase – (“synthesis”) – growth of cell and replication of the DNA G2 phase – (“second gap”) – growth of cell and further preparation for cell division Mitosis – division of a cell’s nucleus Mitosis is a continuum of changes, but for the sake of study it is broken down into the following steps: prophase, metaphase, anaphase, telophase Late interphase Nucleus is well defined 2 centrosomes (each with a pair of centrioles) appear outside of the nucleus Microtubules extend from the centrosomes in radial arrays called asters Chromosomes have already duplicated but are not tightly coiled (they look like a plate of spaghetti) Prophase In the nucleus, the chromatin condenses and can be see with a light microscope The nucleolus (nucleoli) disappear. Each chromosome appears as two sister chromatids Mitotic spindle (microtubules extending from the two centrosomes) begins to form. Centrosomes move away from each other Later in prophase The nuclear envelope dissolves Microtubules of the spindle move across the whole cell and are allowed to interact with the chromosomes (previously protected by the nuclear membrane) Chromosomes are very condensed and attach to a microtubule by a region of the chromosome called a kinetochore Metaphase Centrosomes are at opposite poles. Chromosomes line up on metaphase plate (cell’s equator) Spindle fibers stretch from one end of the cell to the other with the kinetochore attached to the fibers in the middle Anaphase Pair centromeres of each chromosome separate and thus pull apart sister chromatids Chromosomes begin moving to opposite ends of the cell because spindle fibers (microtubules) are shortening. Microtubules without kinetochores begin to lengthen and stretch the cell out By the end of anaphase the chromosomes are at either end of the cell. Telophase and cytokinesis Cell is further elongated Nuclear envelope reappears around the set of chromosomes in each end of the cell Chromatin fiber begins to unwind In animals the cytoplasm is divided in two in a process called cleavage. Plants vs. Animals Cytokinesis in animal cells occurs when a cleavage furrow appears and then the cell pinches in half Cytokinesis in a plant cell occurs when a cell plate forms between the 2 new nuclei. Heredity, Variation and Genetics Heredity is the transmission of traits from one generation to the next. With heredity, in sexually reproducing organisms, comes variation; that is, offspring differ somewhat from parents and siblings Genetics is the study of heredity and variation Genes are heredity units that contain coded information; Genes are segments of DNA; We inherit thousands of them from our parents. Most genes program cells to synthesize specific enzymes and other proteins that produces an organism’s inherited traits. The programming of these traits in the form of DNA is one of the unifying themes of biology A gene’s locus (pl: loci) is the specific location of the gene along the length of a chromosome. Sexual reproduction Results in greater variation Two parents give rise to offspring that have unique combinations of genes inherited from the two parents. Genetic variation is the important consequence Human Life Cycle Somatic cell – any cell other than sperm or ovum has 46 chromosomes Each of the 46 chromosomes has a “match”. That is, another chromosome that is similar (not identical) in length, centromere position, and staining pattern. There are 22 of these pairs and they are called homologous chromosomes (also called homologues). The two chromosomes of each pair of homologues carry genes controlling the same inherited characteristics Autosomes, sex cells and karyotypes Exception to the rule of homologues. There are two chromosomes called X and Y that are sex chromosomes. Human females have a homologous pair X,X. Human males have one X and one Y Any chromosome (the other 44) that is not a sex chromosome is called an autosome The homologues and sex chromosomes are clearly pictured on a karyotype, which is a picture of the chromosomes arranged in pairs from longest to shortest and ending with the sex chromosomes Human male karyotype shown by bright field G-banding of chromosomes: Remember Cells with a full complement of the chromosomes are called diploid (2n). Cells with half of the chromosomes are called haploid (n). Gametes are haploid, somatic cells are diploid. The union of gametes (called fertilization) will result in a zygote with a diploid number Meiosis An overview: Chromosomes duplicate Meiosis I – Homologous chromosome pairs separate Meiosis II – Sister chromatids separate Begin with a diploid cell End with 4 haploid cells Meiosis I - Interphase Interphase – Like mitosis, the chromosomes duplicate, attach together at a centromere and are called sister chromatids. Centrosome also duplicates Prophase I lasts longer and is more complex than prophase in mitosis. The chromosomes condense and homologues, each consisting of two sister chromatids, pair up. Synapsis – a process that uses a protein called synaptonemal complex to attach the homologous chromosomes together. At that point the homologous chromosomes are are together as a tetrad (cluster of four) At various places along their length, the homologous chromosomes are crossed. These crossings are called chiasmata (sing. chiasma). The synaptonemal complex breaks down and the chiasma is what holds the chromosomes together until anaphase I At the chiasma crossing over occurs which increases the genetic diversity of the offspring Like prophase in mitosis, the nuclear membrane begins to break down and the spindle appears. Prophase I can last for days. Occupies 90% of the time required for meiosis Metaphase I The tetrads line up on the metaphase plate Anaphase I Sister chromatids remain attached, but tetrads pull apart and move to opposite poles separating homologous chromosomes Telophase I and Cytokinesis Each pole has a haploid number of chromosomes, but each chromosome has an identical twin because sister chromatids are still attached. Two daughter cells form. Meiosis II Prophase II – a spindle appears Metaphase II – the chromosomes are attached to the spindle like mitosis metaphase Anaphase II – the sister chromatids separate Telophase II and cytokinesis – nuclei form at opposite poles. At the completion of cytokinesis there are four daughter cells each with the haploid number Genetic variation Independent assortment – the tetrad in metaphase I can line up with the maternal homologue on one side or the maternal homologue on the other. It’s a 50/50 chance and they sort randomly and independent of all the other tetrads. The number of combinations possible is represented as 2n with n being the haploid number. Human possibilities 223 or 8 million!! The results of alternative arrangements of two homologous chromosome pairs on the metaphase plate in meiosis I Crossing over Tetrads allow for crossing over which produces recominant chromosomes The results of crossing over during meiosis Random Fertilization Random nature of fertilization adds to genetic variety. 8 million possible female gametes X 8 million possible male gametes = 64 trillion possible offspring from one mating. Regulation of cell cycle Timing and rate of cell division in different parts of a plant or animal are crucial to normal growth, development and maintenance. Skin cells divide frequently; Liver cells only divide for repair; Nerve cells never divide. Cell cycle control is important for us to understand how cells regenerate and how cells lose control of the cell cycle (cancer). Cell cycle control system The cell cycle is regulated using the a set of molecules in the cell that both trigger and coordinate key events in the cell cycle. A key point in the process is the restriction point (R) in G1. If the cell receives the go ahead at that checkpoint it will most likely complete the cell cycle and divide. If not, it will move to G0 state which is a non dividing state. Kinases and cyclin Kinases are proteins that drive the cell cycle. They are present at all times, but only active when attached to a cyclin. A cyclin is a protein that is available in a fluctuating concentration Because of this, the kinases that attach to cyclin are called cyclin-dependent kinases or Cdks. Other regulators Growth factors are proteins that are released by the body’s cells that promote cell division. Ex: PDGF – Platlet –derived growth factors…produced in large amounts at locations of tissue damage, allowing cells to replicate quickly and repair the wound. Preventing over-crowding of cells Lack of growth factors will cause cells to stop dividing. Cells usually do not continue to divide when they become crowded, This is called density-dependent inhibition and results when cells are crowded and stop producing growth factors (perhaps because there is a lack of nutrients) Anchorage Dependence In order to continue dividing cells have to be attached to something such as the inside of a container or the extra cellular matric of a tissue. This is called anchorage dependence. Anchorage dependence and density dependent inhibition help you maintain cells at an optimal density and location. Cancer cells do not respond to control mechanisms. Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence. Scientists believe that cancer cells lack the normal checkpoints in their cell cycle. They will continue to divide as long as nutrients are available. Normal cells will divide 20 to 50 times before they stop dividing, age and die. HeLa cells – cells from a cancer patient (Henrietta Lacks) in culture since 1951 continue to divide today. Henrietta Lacks movie clip Steps in cancer invasion 1. Transformation – normal cell becomes cancer cell. Immune system will usually find these cells and destroy them. 2. If it evades the immune system it can proliferate to become a tumor 3. If the tumor remains at its original site it is called benign and can be removed surgically 4. If the tumor becomes invasive enough to to impair the functions of one or more organs, it is a malignant tumor Malignant tumors are unusual in many ways Excessive proliferation Unusual number of chromosomes Malfunctions in metabolism They lose their attachment to neighboring cells and can easily spread to nearby tissue Can break off and enter the blood and lymph vessels and be carried to other parts of the body This spread of malignant cancer cells is called metastasis (ma-tas-ta-sis).