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 ObjectivesExam 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 process3. 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 PracticeFigure Practice

5

Basic Knowledge Question 1Basic Knowledge Question 1

Which ranking from smallest to largest best fits the sizes of the following molecules:A. sugar nucleotide Gene ChromosomeB. Gene Chromosome sugar nucleotideC. Gene Chromosome nucleotide sugarD. sugar nucleotide Chromosome GeneE. sugar Gene nucleotide Chromosome

6

Annotated FigureAnnotated Figurechromosome

double stranded DNA molecule

Gene

Gene

Nucleotide base-pair

single strand of DNA

7

• 1000-1,000,000 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 chromosomesB. 100s of strands of DNAC. 100s of genesD. 100s of nucleotides

Application Question 2Application 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’)

http://learn.genetics.utah.edu/content/begin/dna/builddna/

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 3Basic Knowledge Question 3

13

DNA DamageDNA 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 4Application Question 4This 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)

1. 2. 3.

1. DNA strands are separated2. Each single strand is used as a template to make a

complementary strand3. Two identical DNA molecules are produced

16

Annotated FigureAnnotated Figurechromosome

double stranded DNA molecule

Gene

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 5Basic Knowledge Question 5

Match these enzymes with their description

I. Ligase

II. Helicase

III. DNA Polymerase

IV. Topoisomerase

1.1. Breaks H-bonds between Breaks H-bonds between nucleotides. nucleotides.

2.2. Creates covalent bonds to Creates covalent bonds to attach nucleotides between attach nucleotides between two fragments of DNA.two fragments of DNA.

3.3. Uses a template strand to Uses a template strand to match complementary bases, match complementary bases, then creates covalent bonds then creates covalent bonds between nucleotides.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 RepairAnything that prevents base-pairing will stop

replication:1. Thymine dimers2. Intercalating agents3. 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.