Download Document

DNA—the thread of life
Biol 100 – K.Marr
1.
Topics this lecture
–
DNA structure and Replication
–
Chapter 10 in Essential Biology by Campbell et al
2.
Lab 7. Modeling DNA Structure, DNA Replication and
Protein Synthesis Read the introduction carefully
–
This week: Part 1 (through page 9)—modeling DNA
Structure and Replication
–
Next week: Part 2—modeling transcription and
translation
Outline for Next few Lectures
Chapter 10—Molecular Biology of the Gene
–
Cystic Fibrosis Case Study
–
Central Dogma of Biology
–
Structure of DNA
–
Replication of DNA
–
Protein Synthesis
•
Transcription = Reading of DNA to make RNA
•
Translation = Reading of mRNA by ribosomes to make protein
Chapter 12—DNA Technology
–
Application of Gene Therapy and biotechnology to cystic fibrosis
Cystic fibrosis—a genetic disease
1. View GATTACA trailer
2. View Cystic Fibrosis Case Study Movie
–
available @ lecture page of class website
3. Optional Reading
–
Cystic Fibrosis Foundation Website:
http://www.cff.org
– Welsh, M.J. and A.E. Smith. Cystic
fibrosis. Scientific American, December
1995
Symptoms of CF
Mucus-clogged
Airways;
Severe
Respiratory
infections
Problems with
digestion due
to clogged
duct from
pancreas
Infertilty in
males due
to clogged
sex ducts
Salty sweat due to
altered salt secretion
in sweat ducts
Lung
Pancreas
Testis
Cell lining ducts
of the body
Cystic Fibrosis: autosomal recessive
Most common lethal genetic disease
–
1 in 2000 children is born with CF in U.S.
–
Untreated children die by age 5
–
Ave. life expectancy: ~27 yrs
–
Special diet + daily dose of antibiotic prevent infection
Carriers of CF gene:
–
Hispanics: 1 in 46
–
African Americans: 1 in 63
–
Asian Americans: 1 in 150
–
Caucasian of European descent: 1 in 25
•
CF allele protects against the plague and many viruses
Cystic Fibrosis


A single faulty protein is connected to the symptoms
In 1989 the gene was mapped to chromosome #7
Our Goal
• To determine the connection between the
symptoms associated with cystic fibrosis and
DNA
• Let’s revisit the central dogma of biology…
Central Dogma of Biology
• Genes interacting with their environment determine
the phenotype of an Organism
Central Dogma of Biology
•
DNA specifies the
synthesis of proteins in
two stages
1. Transcription_____
________________
_______________
DNA
Transcription
Nucleus
RNA
Cytoplasm
2. Translation______
________________
________________
•
Let’s learn a bit about
the structure of DNA
Translation
Protein
DNA is like a rope ladder twisted into a spiral
DNA Structure
• Consists of 2
strands joined
together by weak
hydrogen bonds
• Rungs of the
ladder are
hydrogen bonded
N-bases
Twist
• View Animation of
DNA & RNA
Structure
DNA and RNA: Polymers of Nucleotides
• Nucleotide:
base + sugar +
phosphate
 Note carbon
numbers on
sugar
 Nucleotides join
to form a sugarphosphate
backbone
• Nitrogen
Bases found
in DNA &
RNA
 Uracil replaces
thymine in RNA
Representation of one Strand of DNA
5’ end
Phosphate group
Nitrogenous base
Sugar
Nitrogenous base
(A,G,C, or T)
Nucleotide
Thymine (T)
Phosphate
group
Sugar
(deoxyribose)
3’ end
Polynucleotide
Sugar-phosphate backbone
DNA nucleotide
DNA
Structure
• Complementary
pairing of bases
A to T
and
G to C
• Note 5’ and 3’
ends of each
strand
It’s in the genes...
1.
What’s a gene?
•
Sequence of DNA bases on a chromosome that determines the
amino acid sequence of a protein
2.
The kind of proteins an organism makes helps to determine it’s
phenotype
3.
Genes are...
4.
•
copied during __ S-phase of the cell cycle (DNA replication)_____
•
passed to offspring __during fertilization and when cells divide__
Genes can change or mutate—how?
•
View animation of DNA Replication

available at the lecture section of class website
One DNA molecule before replication
DNA
Replication
(simplified)
5’
3’
Nucleus
3’
DNA polymerase
5’
5’
Parental
strands
Separated by Helicase
3’
5’
3’
Free nucleotides
diffuse in and pair up
with bases on the
Separated strands—
A with T, G with G
Parent strands conserved
After Replication:
2 Identical DNA molecules
5’
3’
5’
DNA polymerase joins
3’ together the newly aligned
nucleotides
5’
3’
5’
New strands formed
(sister chromatids)
3’
DNA
Replication:
DNA
polymerase
can only add
nucleotides
to the 3’ end
of another
nucleotide
a.) Primer binding
b.) Synthesis begins
Two strands of
the parental
DNA molecule
DNA
polymerase
and other
enzymes
Replication
fork moves
Replication
fork
(slide 1 of 2)
3’ end
Primer
(5’ end)
5’ end
Newly made
strands
c.) Replication continues
d.) Replication complete
DNA
Replication
(slide 1 of 2)
Replication
fork moves
This strand is
synthesized
continuously
toward the
fork
Two identical daughter
DNA molecules
This strand is made by
discontinuous synthesis:
Fragments are
synthesized and then
joined together
DNA replication Self-test Questions
1.
When during the cell cycle does it occur?
2.
What do we start with?
3.
What do we end with?
4.
Where in a cell does DNA replication occur?
5.
What’s needed for DNA replication to occur?
6.
What is the sequence of events?
7.
Why is DNA replication said to be semi-conservative?
8.
What does proofreading mean in terms of DNA replication?
9.
What does the proofreading during DNA replication?
How do nucleotide analogues work to stop DNA
replication in cancer cells and HIV?
The drug AZT, below, is effective at preventing the
spread of HIV. How?
Thymine
(T)
AZT
Part of a Thymine nucleotide
DNA can be damaged by ultraviolet light
1. Enzymes (e.g. DNA polymerase) can repair the
damage.
–
Is the damage always repaired? Consequences?
2. Why does burnt skin peel? What gene is involved?
3. Role of Apoptosis?
4. Role of p53 gene?
–
Advantages of peeling?
–
Disadvantages?