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Group Project 5: Cancer: What are my options? What are you? A Techie? What would you need to know? Project: You group will be creating a graphic to describe a chemotherapy drug and use the information you find advise someone about how this drug works and how effective it is at treating cancer. • Your biggest challenge will be to explain the complexities of how your drug works without overwhelming the reader with jargon. But, you will also need to explain the most likely outcome of taking this drug compared to either no treatment or other treatments in a way that is sensitive. Imagine you are helping a loved one make an informed decision about using this treatment option. • Figures and graphs will be very important 2 Learning Objectives Exam questions will tested understanding of: 1. Basic structure of DNA • Composed of two chains of bonded nucleotides that are complementary (A-T, G-C) and of opposite polarity (anti-parallel) • Difference between gene, nucleotide, DNA, a chromosome, and two identical copies of a chromosome. 2. How DNA is replicated • Major enzymes involved, their functions, and how interfering with enzymes effects the process 3. How DNA is damaged and repaired (intercalating agents, thymine dimers, excision repair) 3 Figure Practice Label this picture: 1. Chromosome 2. Double-stranded DNA double helix 3. Single strand of DNA 4. Single gene 5. Nucleotide base pair 4 Basic Knowledge Question 1 Which ranking from smallest to largest best fits the sizes of the following molecules: A. B. C. D. E. sugar Gene Gene sugar sugar nucleotide Gene Chromosome Chromosome sugar nucleotide Chromosome nucleotide sugar nucleotide Chromosome Gene Gene nucleotide Chromosome 5 Annotated Figure chromosome single strand of DNA Nucleotide base-pair double stranded DNA molecule 6 DNA Damage • 10001,000,000 lesions/day • Why is this a problem? •Cellular Metabolic processes create reactive oxygen species (free radicals that attack covalent bonds) •UV-A light: free radicals/ UV-B light: thymine dimers (cross-linking) •Ionizing radiation X-rays: double strand breaks •Chemicals: polycyclic hydrocarbons (smoke, soot, tar), intercalating 7 agents (thalidomide, aflotoxin B) squeeze between base pairs in DNA Application Question 2 This picture shows DNA damage due to ionizing radiation. The arrows show breaks in the DNA. The cell containing this DNA could potentially lose: A. Whole chromosomes B. 100s of strands of DNA C. 100s of genes D. 100s of nucleotides 8 DNA Monomer = Nucleotides three parts { •Phosphate group •Sugar (deoxyribose) •Nitrogenous base 9 Nucleic Acids •Nucleotides connected through covalent bonds between sugar and phosphate •Distinct ends •Phosphate (5’) •Sugar (3’) •Nitrogenous bases can interact with bases on other chains to make double helix http://learn.genetics.utah.edu/content/begin/dna/builddna/ 10 Hydrogen Bonds •Base pairs •A-T •G-C •complementary •Antiparallel 11 Basic Knowledge Question 3 Which of the following is a correct statement about DNA structure? A. DNA is composed of two complementary and parallel strands. B. The DNA backbone is made up of repeating units of sugar-nucleotides. C. The nitrogenous bases of DNA are adenine, guanine, cytosine, and uracil. D. The nitrogenous bases pair as follows: adenine with thymine, cytosine with guanine. E. All of these statements about DNA structure are 12 correct. DNA Damage label the location of intercalating agents that fit between base pairs and unwind the double helix: label the location of a possible thymine dimer (crosslink): label the location of double strand break: 13 Many chemotherapy agents stop replication (intercalators, crosslinkers) Application Question 4 This picture shows the formation of a thymine dimer after exposure to UV-B light. Which of the following bonds CAN’T occur because of this: A. Covalent bonds between adjacent nucleotides in the same strand of DNA B. Hydrogen bonds between adjacent nucleotides in the same strand of DNA C. Hydrogen bonds between complementary nucleotides in the two antiparallel strands of DNA 14 Hydrogen Bonds between base pairs serves as basis for mechanism of Copying DNA (Replication) 1. 2. 3. 1. DNA strands are separated 2. Each single strand is used as a template to make a complementary strand 3. Two identical DNA molecules are produced 15 Annotated Figure Label this picture: chromosome 1. Identical duplicate parts of the same chromosome 2. Show original DNA helix unwound with two new daughter strands in blank single strand of DNA space. Nucleotide base-pair double stranded DNA molecule 16 Enzymes Perform Replication • Topoisomerases untwists DNA double helix • Helicases removes H-bonds holding two strands together. • DNA polymerase connects new complementary bases. • DNA ligase fills in any small gaps between adjacent nucleotides so that fragments are attached into one single strand Many chemotherapy agents stop replication (topoisomerases) 17 Enzymes Perform Replication & Repair 18 Basic Knowledge Question 5 Match these enzymes with their description I. II. III. IV. A. B. C. D. Ligase Helicase DNA Polymerase Topoisomerase I, 4; II, 3; III, 2; IV, 1 I, 2; II, 1; III, 3; IV, 4 I, 2; II, 4; III, 1; IV, 3 I, 3; II, 2, III, 1; IV, 4 1. Breaks H-bonds between nucleotides. 2. Creates covalent bonds to attach nucleotides between two fragments of DNA. 3. Uses a template strand to match complementary bases, then creates covalent bonds between nucleotides. 4. Unwinds double helix 19 Excision Repair Anything that prevents base-pairing will stop replication: 1. Thymine dimers 2. Intercalating agents 3. Missing nucleotide or incorrect base pair Errors must be excised and repaired using often the same replication enzymes. Un-repaired damage or incorrectly repaired damage in rapidly dividing cells leads to mutations. Un-repaired damage in slowly dividing cells accumulates and leads to cancer. 20