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Transcript
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