Group Project 5: Cancer: What are my options? What are you? A Techie?

2 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 What would you need to know?

3 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)

4 Label this picture: 1.Chromosome 2.Double-stranded DNA double helix 3.Single strand of DNA 4.Single gene 5.Nucleotide base pair Figure Practice

5 Basic Knowledge Question 1 Which ranking from smallest to largest best fits the sizes of the following molecules: A.sugar nucleotide Gene Chromosome B.Gene Chromosome sugar nucleotide C.Gene Chromosome nucleotide sugar D.sugar nucleotide Chromosome Gene E.sugar Gene nucleotide Chromosome

6 Annotated Figure chromosome double stranded DNA molecule Gene Nucleotide base-pair single strand of DNA

,000,000 lesions/day Why is this a problem? DNA Damage 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 agents (thalidomide, aflotoxin B) squeeze between base pairs in DNA

8 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 Application Question 2

9 DNA Monomer = Nucleotides Phosphate group Sugar (deoxyribose) Nitrogenous base { three parts

10 Nucleic Acids Nucleotides connected through covalent bonds between sugar and phosphate Nitrogenous bases can interact with bases on other chains to make double helix Distinct ends Phosphate (5’) Sugar (3’)

11 Hydrogen Bonds Base pairs A - T G - C Antiparallel complementary

12 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 correct. Basic Knowledge Question 3

13 DNA Damage label the location of a possible thymine dimer (crosslink): label the location of double strand break: label the location of intercalating agents that fit between base pairs and unwind the double helix: Many chemotherapy agents stop replication (intercalators, crosslinkers)

14 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

15 Hydrogen Bonds between base pairs serves as basis for mechanism of Copying DNA (Replication) 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

16 Annotated Figure chromosome double stranded DNA molecule Gene Nucleotide base-pair single strand of DNA Label this picture: 1.Identical duplicate parts of the same chromosome 2.Show original DNA helix unwound with two new daughter strands in blank space.

17 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)

18 Enzymes Perform Replication & Repair

19 Basic Knowledge Question 5 Match these enzymes with their description I.Ligase II.Helicase III.DNA Polymerase IV.Topoisomerase 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 A.I, 4; II, 3; III, 2; IV, 1 B.I, 2; II, 1; III, 3; IV, 4 C.I, 2; II, 4; III, 1; IV, 3 D.I, 3; II, 2, III, 1; IV, 4

20 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.