Cell growth and division Dr. Piyapat Pin-on Objectives • Describe cell growth and division in eukaryote: mitosis and meiosis. • Describe molecular mechanism for regulating mitotic events and checkpoints in cell-cycle regulation. Learning Objectives Explain the problems that growth causes for cells. Compare asexual and sexual reproduction. Limits to Cell Growth • The larger a cell becomes, the more demands the cell places on its DNA and the more trouble the cell has moving enough nutrients and wastes across the cell membrane. • Two reasons why cell size is limited: • If a cell were to grow without control, DNA overload would occur. • Rate of material exchange is dependent on surface area http://www.youtube.com/watch?v=xuG4ZZ1GbzI I. Cell Growth A. A living thing grows because it produces more and more cells. 1. The cells of a human adult are no larger than the cells of a human baby, but there are more of them. 2. The smaller the cell the better it is. The larger the cell the more difficult to perform cellular functions. 3. Cell division is the process whereby the cell divides into two daughter cells. Limits to Cell Growth • As a cell grows larger: • More demands are put onto the cell’s DNA. • The cell has more trouble moving enough nutrients and wastes across the cell membrane. • A cell’s functions are controlled by its DNA. • As a cell grows, it usually does not make more DNA. • If the cell were to grow continuously, it would become too large for the DNA to control...this is called “DNA Overload”. • Materials such as food, oxygen, waste and water pass in and out of a cell through the cell membrane. • The rate at which materials can pass through the membrane depends on the cell’s surface area. • The rate at which food and oxygen are used and waste is produced depends on the cell’s volume. • To maintain high efficiency, cells maintain a large surface area to volume ratio. • Imagining that cells are cube-shaped, look at the example below: Which value increases most rapidy? How does the SA:V ratio change as the cell Cell Division • Before a cell becomes too large, it divides into two daughter cells by a process called cell division. II. Cell Division A. The first stage of cellular division in Eukaryotes is called mitosis. The second stage is called cytokinesis. B. Chromosomes 1. In Eukaryotic cells, chromosomes carry the genetic information that is passed on from one generation of cells to the next. C. The cell cycle 1. The cell cycle describes the life of a Eukaryotic cell. 2. The cell cycle is a repeating sequence of cellular growth and division during the life of an organism. 3. A cell spends 90% of its time in the first three phases of the cycleInterphase. 4. First growth (G1)phase- a cell grows rapidly and carries out its routine functions. Cells that are not dividing remain in the G1 phase. 5. Synthesis (S) phase- A cell’s DNA is copied during this phase. At the end of this phase, each chromosomes consists of two chromatids attached at the centromere. 6. Second growth (G2) phase-In the G2 phase, preparations are made for the nucleus to divide. 7. Mitosis- The process during cell division in which the nucleus of a cell is divided into two nuclei. 8. Cytokinesis- the cytoplasm splits. Controls on Cell Division • Effects of controlled cell growth can be seen by placing some cells in a petri dish containing nutrient broth • Cells grow until they form a thin layer covering the bottom of the dish • Cells stop growing when they come into contact with other cells • If cells are removed, the remaining cells will begin dividing again • Something can turn cell division on or off Regulating Cell Growth • Cyclins- proteins that regulate the timing of the cell cycle in eukaryotic cells • Internal regulators: proteins that respond to events inside the cell • i.e. make sure all chromosomes have been replicated; make sure all chromosomes are attached to the spindle before entering anaphase • External regulators: proteins that respond to events outside the cell • i.e. embryonic development; wound healing D. The cell cycle is carefully controlled. 1. If a cell spends 90% of its time in interphase, how do cells “know” when to divide? 2. Cell Growth (G1) checkpoint-This checkpoint makes the key decision of when the cell will divide or not. 3. DNA synthesis (G2) checkpoint-DNA replication is checked at this point by DNA repair enzymes. If this checkpoint is passed, proteins help to trigger mitosis. 4. Mitosis check point- will trigger the exit from mitosis. B. Cell cycle regulators. 1. For many years scientists are looking for something that can regulate the cell cycle. 2. It was discovered that a protein cyclin regulated the cell cycle. 3. Cyclin regulate the timing of the cell cycle in Eukaryotic cells. 4. It was also discovered that there are two types of regulator proteins 1- those that occur inside of the cell and 2- those that occur outside of the cell. C. Internal regulators 1. Proteins that respond to events inside the cell are called internal regulators. 2. Internal regulators that allow the cell cycle to proceed only when certain processes have happened inside of the cell. D. External regulators 1. Proteins that respond to events outside the cell are called external regulators. 2. External regulators direct ells to speed up or slow down the cell cycle. 3. Growth factors are among the most important external regulators. 4. They stimulate the growth and division of cells. 5. Growth regulators are very important in embryonic development and wound healing. Regulating the Cell Cycle •Experiments show that normal cells will continue to grow until they come into contact with other cells. •When cell’s come into contact with other cells, they stop growing. This is called contact inhibition. •This demonstrates that cell growth and division can be turned on and off. Regulating the Cell Cycle Learning Objectives Describe how the cell cycle is regulated. Explain how cancer cells are different from other cells. The Discovery of Cyclins • Scientists found a protein in a cell undergoing mitosis. • They injected the protein into a non-dividing cell. • A mitotic spindle started to form. • Cyclins: proteins that regulate the cell cycle Regulatory Proteins Internal regulators: • respond to events inside the cell • let cell cycle proceed only when certain steps have already happened External regulators: • respond to events outside the cell • direct cells to speed up or slow down the cell cycle • growth factors: wound healing and embryonic development Cdk (cyclin dependent kinase, adds phosphate to a protein), along with cyclins, are major control switches for the cell cycle, causing the cell to move from G1 to S or G2 to M. MPF (Maturation Promoting Factor) includes the CdK and cyclins that triggers progression through the cell cycle. p53 is a protein that functions to block the cell cycle if the DNA is damaged. If the damage is severe this protein can cause apoptosis (cell death). p53 levels are increased in damaged cells. This allows time to repair DNA by blocking the cell cycle. A p53 mutation is the most frequent mutation leading to cancer. An extreme case of this is Li Fraumeni syndrome, where a genetic a defect in p53 leads to a high frequency of cancer in affected individuals. p27 is a protein that binds to cyclin and cdk blocking entry into S phase. Recent research (Nature Medicine 3, 152 (1997)) suggests that breast cancer prognosis is determined by p27 levels. Reduced levels of p27 predict a poor outcome for breast cancer patients. Contact Inhibition Copyright Pearson Prentice Hall • Proteins called cyclins regulate the timing of the cell cycle. • Internal regulators: allow the cell to proceed to the next phase of the cell cycle only when certain processes have occurred inside the cell. • Example: These proteins will not allow a cell to continue into G2until all chromosomes have been duplicated during S phase. • External regulators: speed up or slow down the cell cycle depending on events outside of the cell. • Example: Contact inhibition The Cell-Cycle Control System Depends on Cyclically Activated Cyclin-Dependent Protein Kinases (Cdks) THE CELL-CYCLE CONTROL SYSTEM Cdk Activity Can Be Suppressed By Inhibitory Phosphorylation and Cdk Inhibitor Proteins (CKIs) Regulated Proteolysis Triggers the Metaphase-toAnaphase Transition Cell-Cycle Control Also Depends on Transcriptional Regulation The Cell-Cycle Control System Functions as a Network of Biochemical Switches Uncontrolled Cell Growth • Cancer- a disorder in which some of the body’s own cells lose the ability to control growth. • Disease of the cell cycle E. Uncontrolled cell growth. 1. Why is cell growth regulated so carefully? 2. Cancer is a consequence of uncontrolled cell growth. 3. Cancer is a disorder in which some of the body’s own cells lose the ability to control growth 4. Cancer cells do not respond to the signals that regulate the growth of most cells. 5. As a result, they divide uncontrollably and form masses of cells called tumors that can damage the surrounding tissues. 6. Cancer cells may break loose from tumors and spread throughout the body, disrupting normal activities and causing serious medical problems or even death. 7. There are certain carcinogens that can cause this to happen. Such as: tobacco, radiation exposure, and even a viral infection. 8. Cancer is a disease of the cell cycle, and conquering cancer will require a much deeper understanding of the processes that control cell division. Uncontrolled Cell Growth • Cancer is a disorder in which the body’s own cells lose their ability to respond to signals from internal and external regulators. • These cells divide uncontrollably and form tumors. Cancer: Uncontrolled Cell Growth • Cancer cells don’t respond to normal regulatory signals. • Cell cycle is disrupted. • Cells grow and divide uncontrollably. tumor blood vessel Cancer Formation: A Closer Look 1. A cell begins to divide abnormally. 2. Cells produce a tumor and start to displace normal cells and tissues. 3. Cancer cells move to other parts of the body. What Causes Cancer? In all cancers, control over down. the cell cycle has broken Cancer results from a defect in genes that control cell growth and division. Treatments for Cancer • Surgery to remove localized tumor • Radiation to destroy cancer cell DNA • Chemotherapy to kill cancer cells or slow their growth The Process of Cell Division Learning Objectives Describe the role of chromosomes in cell division. Name the main events of the cell cycle. Describe what happens during the four phases of mitosis. Describe the process of cytokinesis. The structure of a chromosome • Chromatin • Chromatid • Centromere • Chromosomes are not visible in most cells except during cell division. • At the beginning of cell division the chromosomes condense into compact, visible structures that can be seen under a light microscope. The Chromosome • Chromosome: “X” shaped cell structure that directs cell activities and passes on traits to new cells. • Each identical strand of the chromosome is called a chromatid. • The strands are held together by a structure called the centromere. • Chromatin: Loosely coiled DNA Parts of a Chromosome The Cell Cycle • Interphase • G1 Phase: Cell Growth • S Phase: DNA Replication • G2 Phase: Preparation for Mitosis • Prophase • Metaphase • Anaphase • Telophase • Cytokinesis Interphase: G1 • Cell Grows • Synthesis of proteins and new organelles S-Phase • Chromosomes are duplicated and the synthesis of DNA molecules takes place. G2 Phase • Many of the organelles and molecules required for cell division are produced. • The cell is then ready to enter MPhase to begin the process of Cell division Interphase • 3 phases • G1 phase= cells do most of their growing • Increase in size and synthesize new proteins and organelles • S phase= chromosomes are replicated and the synthesis and DNA molecules takes place • Usually if a cell enters S phase and begins replication, it completes the rest of the cycle • G2 phase= many of the organelles and molecules required for cell division are produced • Shortest of the 3 phases of interphase Mitosis • Divided into 4 phases • • • • Prophase Metaphase Anaphase Telophase • Followed with Cytokinesis • Depending on cell- may last a few minutes to several days The Principle Stages of M Phase (Mitosis and Cytokinesis) in an Animal Cell Prophase • The chromatin condense into chromosomes. • The centrioles separate and a spindle begins to form. • The nuclear membrane breaks down. Prophase • 1st and longest phase of mitosis • Events • Chromosomes become visible • Centrioles separate and move to opposite sides of the cell • Chromosomes become attached to fibers in the spindle at the centromere • Chromosomes coil more tightly • Nucleolus disappears • Nuclear envelope breaks down Prophase • First and longest phase of Mitosis. Spindle forming • Chromosomes condense and become visible. • Centrioles move to opposite sides of the nucleus. • Spindle appears. • Nucleolus disappears. Centromere Chromoso mes (paired Prophase The nucleus condenses and chromosomes become visible. The spindle begins to form. Metaphase • The chromosomes line up along the middle of the cell. • “M”eet in the “M”iddle! • Each chromosome is connected to a spindle fiber at its centromere. Metaphase • Often lasts only a few minutes • Events • Chromosomes line up across the center of the cell • Microtubules connect the centromere of each chromosome to the two poles of the spindle • Chromosomes are made up of DNA and protein. • Before prophase, they are not visible because their thin strands are spread throughout the nucleus. • During S phase, the chromosomes are replicated. • Once replication has occurred, each chromosome consists of 2 “sister” chromatids, which are held together at a centromere. Metaphase Centriole • Second phase of mitosis. • Chromosomes line up across the center of the cell. • Spindles attach to the centromere of each chromosome, connecting them to the centrioles and holding them in place. Spindle Metaphase Chromosomes line up at the center of the cell. chromati d centriole s centrom ere chromos ome Anaphase • The sister chromatids separate into individual chromosomes and move apart. • Anaphase pulled Apart Anaphase • Centromeres split • Sister chromatids separate and move to opposite poles • Anaphase ends when chromosomes stop moving Anaphase • Third phase of mitosis. • The centromeres split allowing the sister chromatids to separate. • Spindles pull the sister chromatids to opposite sides of the cell. Individual chromosomes Anaphase Chromosomes move toward opposite poles. individual chromosomes Telophase • The chromosomes gather at opposite ends of the cell and lose their distinct shapes. • Two new nuclear membranes form • Two new Nuclei Telophase • Chromosomes begin to disperse into a chromatin • Nuclear envelope re-forms around each cluster of chromosomes • Spindle begins to break apart • Nucleolus becomes visible Telophase • Final phase of Mitosis. • Chromosomes unravel • Nuclear envelopes reform • Nucleolus reappears • Spindle begins to break apart. Telophase The cell begins to divide into daughter cells. nuclear envelopes re-forming Cytokinesis • The cell membrane pinches the cytoplasm in half. • Each daughter cell has an identical set of duplicate chromosomes. Cytokinesis • Occurs at the same time as telophase • Animal cells: • Cell membrane is drawn inward until the cytoplasm is pinched into 2 nearly equal parts • Plant cells: • Cell plate forms midway between the divided nuclei • Cell wall begins to appear in the cell plate • Result? 2 new identical cells Cytokinesis • Mitosis is considered to be the division of the nucleus. • After mitosis, two nuclei with identical sets of chromosomes are present within the cytoplasm of a single cell. • Cytokinesis is the division of the cytoplasm, which completes M Phase of the cell cycle. Cytokinesis • Usually occurs simultaneously with telophase. • In animal cells: • The cell membrane is pulled inward until the cytoplasm is pinched in equal parts. • In plant cells: • A “cell plate” forms midway between the two new nuclei. The plate will eventually develop into a cell wall dividing the two cells. Cytokinesis In animal cells, the cell membrane pinches in the center to form two daughter cells. Length of the Cell Cycle of a Human Liver Cell • Interphase: 21 hours • Growth : 9 hours • DNA Replication: 10 hours • Preparation for Division: 2 hours • Mitosis: 1 hour • • • • Prophase Metaphase Anaphase Telophase Sexual Reproduction • Sexual reproduction involves the parent cells. fusion of two separate • Offspring inherit some genetic information from each parent. Comparing Asexual and Sexual Reproduction Asexual Produce many offspring in short period Don’t need to find a mate In stable environments, genetically identical offspring thrive. If conditions change, offspring not well adapted. Sexual Relatively fewer offspring; growth takes more time Need to find a mate In changing environments, genetic diversity can be beneficial. Offspring may be less well adapted to current conditions. Homolog Segregation Depends on Several Unique Features of Meiosis I CONTROL OF CELL DIVISION AND CELL GROWTH Mitogens Stimulate G1-Cdk and G1/S-Cdk Activities Cells Can Enter a Specialized Nondividing State Cell Proliferation is Accompanied by Cell Growth Proliferating Cells Usually Coordinate Their Growth and Division Learning Check • Name the main events of the cell cycle. • What happens during each stage of interphase? • What are chromosomes made of? • At the completion of M Phase (Mitosis and Cytokinesis), two identical daughter cells have formed. • These two daughter cells restart the cell cycle at G1 of interphase.