Chapter 12 Notes Introduction Cell division: the continuity of life based on the reproduction of cells Cell division plays several important roles in the life of an organism o Can produce progeny from multicellular organisms (ex: plants growing from cuttings) o Enables sexually reproducing organisms to develop from a single cell o Continues to function in renewal and repair Cell cycle: o The life of a cell from the time it is first formed from a dividing parent cell until its own division into two cells 12.1 Cell division results in genetically identical daughter cells Cell division involves the distribution of identical genetic material (DNA) to two daughter cells o A dividing cell duplicates its DNA, allocates the two copies to opposite ends of the cell, and then splits into two daughter cells Cellular Organization of the Genetic Material Genome: cell’s allotted DNA (its genetic information) o Prokaryotic genome is one DNA molecule o Eukaryotic genome usually several DNA molecules Length is about 2M in adult human cells Chromosomes: the structure DNA is packed into o Every eukaryotic species has a characteristic number of chromosomes in the nucleus Somatic cells: all body cells except reproductive cells o In humans, somatic cells contain 46 chromosomes made of two sets of 23 One set inherited from each parent Gametes: reproductive cells; sperm and egg cells o Contain half as many chromosomes as somatic cells In humans, 23 chromosomes Chromatin: complex of DNA and associated protein molecules o Makes up chromosomes Each chromosome contains one very long, linear DNA molecule that carries several hundred to a few thousand genes o Genes: the units that specify an organism’s inherited traits The associated protein molecules maintain the structure of the chromosome and help control the activity of the genes Distribution of Chromosomes During Cell Division When a cell is not dividing, each chromosome is in the form of a long, thin chromatin fiber o After DNA duplication, the chromosome condense Each chromatin fiber becomes densely coiled and folded, making the chromosomes much shorter and thicker Sister chromatids: pair of duplicated chromosomes o The two chromatids are attached to each other at the centromere Contain an identical DNA molecule Once sister chromatids separate, they are called chromosomes Mitosis: the division of the nucleus Cytokinesis: the division of the cytoplasm Chromosome number through generations: o You inherit 46 chromosomes from parents (23 from each parent) 23 from sperm cell; 23 from egg cell o Mitosis and cytokinesis produced 200 trillion somatic cells that now make up your body o You produce gametes by a process called meiosis Meiosis yields nonidentical daughter cells that have only one set of chromosomes, so it has half as many chromosomes as the parent cell Meiosis only occurs in your gonads o In each generation of humans, meiosis reduces the chromosome number from 46 (two sets of chromosomes) to 23 (one set) o Fertilization fuses the two gametes together to return the chromosome number to 46 12.2 Phases of the Cell Cycle Mitotic phase: includes mitosis and cytokinesis o Shortest part of the cell cycle o Alternates with interphase Interphase: 90% of cell cycle o Cell grows and copies its chromosomes in preparation for cell division Divided into subphases: G1 phase: first gap S phase: synthesis G2 phase: second gap o During all subphases, cell grows by producing proteins and organelles (ex: mitochondria, ER) o Chromosomes duplicated only during S phase o So, cell grows (G1), grows and copies chromosomes (S), and grows as preparations for cell division is complete (G2), and divides (M) Cell undergoes one division in 24 hours o M phase occupies less than an hour o S phase occupies 10-12 hours (half) o G2 occupies 4-6 hours o G1 occupies 5-6 hours Mitosis broken down into five stages: o Prophase o Prometaphase o Metaphase o Anaphase o Telophase Cytokinesis completes mitotic phase The Mitotic Spindle: A Closer Look Mitotic spindle: begins to form in the cytoplasm during prophase o Consists of fibers made of microtubules and associated proteins o When spindles assembles, the other microtubules of the cytoskeleton partially disassemble Centrosome: nonmembranous organelle that functions throughout the cell cycle to organize the cell’s microtubules o Pair of centrioles is located at the center of the centrosomes Centrioles not essential for cell division During interphase, the single centrosome replicates, forming two centrosomes which remaine together near the nucleus o Centrosomes move apart during prophase and prometaphase By the end of prometaphase, the two centrosomes are at opposite ends of the cell Aster: radial array of short microtubules, extends from each centrosome o Spindle includes: Centrosomes Spindle microtubules Asters Kinetochore: structure of proteins associated with specific sections of chromosomal DNA at the centromere o Associated with sister chromatids o Two kinetochores face in opposite directions During prometaphase, spindle microtubules attach to kinetochores When a kinetochore is “captured” by microtubules, the chromosome begins to move toward the pole from which those microtubules extend o Then, microtubules from opposite pole attach to other kinetochore Chromosome moves in one direction and then the other until they are halfway in the middle of the cell In metaphase, centromeres of all duplicated chromosomes are on a plane midway between the poles o Metaphase plate: imaginary plane Microtubules that do not attach to the kinetochores have been growing, and by metaphase, they overlap and interact with other nonkinetochore microtubules from the opposite poles of the spindle Anaphase: starts suddenly when proteins holding together the sister chromatids are inactivated o Once the chromatids separate, (now full chromosomes) they move toward opposite ends of the cell How? Two possibilities: o Chromosomes are “reeled in” by microtubules that are shortening at the poles o Motor proteins on the kinetochores “walk” a chromosome along the attached microtubules toward the nearest pole Meanwhile, the microtubules shorten Function of nonkinetochore microtubules: responsible for elongating the whole cell during anaphase o In metaphase, these microtubules from opposite poles overlap each other In anaphase, the region of overlap is reduced as motor proteins attached to the microtubules walk them away from one another Do this by using energy from ATP At the end of anaphase, duplicate groups of chromosomes have arrived at opposite ends of the elongated parent cell Nuclei re-form during telophase Cytokinesis: A Closer Look In animal cells, cytokinesis occurs by a process known as cleavage First sign of cleavage is the appearance of a cleavage furrow o Cleavage furrow: shallow groove in the cell surface near the old metaphase plate On cytoplasmic side of furrow is a contractile ring of actin microfilaments associated with molecules of myosin o Actin microfilaments interact with the myosin molecules, causing the ring to contract Contraction of ring is like pulling drawstrings Cleavage furrow deepends until the parent cell is pinched in two In plant cells, cytokinesis occurs using a cell plate o During telophase, vesicles from the Golgi apparatus move along microtubules to the middle of the cell, where they join to produce a cell plate Cell plate enlarges until its surrounding membrane fuses with the plasma membrane along the perimeter of cell Binary Fission Prokaryotes reproduce by binary fission o In bacteria, most genes are carried on one chromosome that consists of a circular DNA molecule and associated proteins In E. coli, the process of cell division begins when the DNA of the bacterial chromosome begins to replicate at a specific place on the chromosome called the origin of replication o This produces two origins o As the chromosome continues to replicate, one origin moves rapidly toward the opposite end of the cell While the chromosome replicates, the cell elongates When replication is complete, the plasma membrane grows inward, dividing the parent cell into two cells In most bacterial species, the origins of replication end up at opposite ends of the cell The Evolution of Mitosis Mitosis had its origins in simpler prokaryotic mechanisms of cell reproduction o Some proteins involved in binary fission are related to eukaryotic proteins Hypothesis for stepwise evolution of mitosis o Intermediate stages represented by two unusual types of nuclear division found in certain modern unicellular protists 12.3 The cell cycle is regulated by a molecular control system Frequency of cell division varies with type of cell Evidence for Cytoplasmic Signals What drives the cell cycle? o Original hypothesis: each event in the cell cycle signals the next Ex: replication of chromosomes in the S phase might cause cell growth during the G2 phase o New hypothesis: the cell cycle is driven by molecular signals present in the cytoplasm Experiment caused two cells at two different points in the cell cycle to fuse When S cell fused with G1 cell, G1 cell immediately switched to S phase Concluded that there must be something in cytoplasm to trigger this response The Cell Cycle Control System Cell cycle control system: cyclically operating set of molecules in the cell that both triggers and coordinates key events in the cell cycle o Proceeds on its own, driven by a built-in clock o Cell cycle is regulated at certain checkpoints by both internal and external controls Checkpoint: critical control point where stop and go-ahead signals can regulate the cycle o Animal cells have stop signals that halt the cell cycle at checkpoints until overridden by go-ahead signals Signals report whether crucial cellular processes up to that point have been completed correctly o Three major checkpoints: G1 G2 M G1 checkpoint: called restriction point o Most important o Go ahead: moves to S, G2, and M phases and then divides o Stop: exit the cycle and switch to G0 phase G0 phase: nondividing state Most cells are actually in G0 stage Ex: nerve cells, liver cells The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases o Fluctuations in the amount and activity of cell cycle control molecules pace the stages of the cell cycle These regulatory molecules are proteins of two main types: kinases and cyclins Protein kinases: enzymes that activate or inactivate other proteins by phosphorylating them o Some give the go-ahead signals at the G1 and G2 checkpoints Kinases are actually present at a constant concentration in the growing cell o Spend most of their time in active form To be active, must be attached to a cyclin Cyclin: a protein that gets its name from its cyclically fluctuating concentration in the cell o Together, they’re called cyclin-dependent kinases (Cdks) Activity of Cdks rises and falls with changes in concentration of cyclin o MPF: maturation-promoting factor Peaks in correlation to peaks in cyclins Rises during S and G2 phases; falls during mitosis o When cyclins that accumulate during G2 associate with Cdks molecules, the resulting MPF complex initiates mitosis MPF acts as a kinases and indirectly by activating other kinases o During anaphase, MPF helps switch itself off by initiating a process that leads to the destruction of its own cyclin Stop and Go Signs: Internal and External Signals at the Checkpoints o Scientists know that in general, active Cdks function by phosphorylating substrate proteins that affect particular steps in the cell cycle o Example of internal signal: M phase checkpoint Anaphase does not begin until all the chromosomes are properly attached to the spindle at the metaphase plate Kinetochores send a molecular signal that causes the sister chromatids to remain together, delaying anaphase Only when the kinetochores of all chromosomes are attached to the spindle will the sister chromatids separate o Researchers have been able to identify external factors (chemical and physical) that can influence cell division Ex: cells don’t divide if an essential nutrient is left out Most cells divide if only certain types of growth factors are present Growth factor: protein released by certain cells that stimulates other cells to divide o Ex: platelet-derived growth factor Made by platelets Required for the division of fibroblasts Fibroblasts: type of connective tissue cells PDGF binds to receptors on membrane of fibroblasts triggers a signal transduction pathway that allows the cells to pass the G1 checkpoint and divide o 50 different growth factors can trigger cells to divide o Effect of an external physical factor seen in density-dependent inhibition, a phenomenon in which crowded cells stop dividing If you culture cells in a petri dish, they will divide until they form a single layer If you remove some, cells will divide again until dish is full Growth factors and nutrients available to each cell affects how many cells there can be in an environment o Anchorage dependence Must be attached to a substratum Loss of Cell Cycle Controls in Cancer Cells Cancer cells do not respond normally to the body’s control mechanisms o They divide excessively and invade other tissues If unchecked, they can kill Cancer cells do not heed the normal signals that regulate the cell cycle o Do not exhibit density-dependent inhibition o Do not stop growing when growth factors are depleted Because growth factors from a cell’s cytoplasm are not needed for cancer cells to grow Cells may make their own growth factors, or there is an error in the cell signaling pathway (conveys signal of growth factor even though there isn’t one present) Differences between cancer and regular cell cycles o Cancer cells divide and stop dividing at random points in the cycle o Cancer cells can go on dividing indefinitely if given continual supply of nutrients Normal cells divide 20-50 times before they stop dividing Transformation: process that converts a normal cell to a cancer cell o Immune system normally identifies the transformed cell and kills it But, if it’s not destroyed, it can form a tumor Benign tumor: abnormal cells remain at the original site o Do not cause serious problems and can be completely removed by surgery Malignant tumor: becomes invasive enough to impair the functions of one or more organs o Classifies a person as having cancer o Cells of a malignant tumor have unusual numbers of chromosomes; metabolism may be disabled; cease to function in constructive way; lose or destroy attachments to neighboring cells; can spread into nearby tissues; secrete signal molecules that cause blood vessels to grow toward the tumor Metastasis: spread of cancer cells to locations distant from their original site o Cancer cells travel through blood and lymph vessels to other parts of the body Localized tumor treated with radiation o Damages DNA in cancer cells more than normal cells To treat metastatic tumors, chemo is used o Drugs that are toxic to actively dividing cells are administered through the circulatory system Interfere with specific steps in cell cycle