MOLECULAR STRUCTURE OF DNA & RNA AND THE CONSEQUENCES
CHAPTER 9
DNA’s role in medical science
● genetic disease
○ gene regulation
● cancer
● diagnostics
● genetic therapies
○ based on DNA/RNA
● DNA damage/damaging agents
● research
○ gene expression and modification
Roles of the Genetic Material
● Francis Crick
● genetic material has two jobs
○ duplicate
○ development control
Genetic Material Criteria
1. information
a. to make organism
2. transmission
a. parent to offspring
3. replication
a. copy
i. to pass from cell to cell
4. variation
a. changing
i. phenotypic variation
ii. adaptation and evolution
Friedrich Miescher Discovered DNA
● called ‘nuclein’ ⇒ now DNA
Evidence of DNA Being Responsible for Inheritance - Transmitting Traits
1. bacterial pathogens
2. viruses
Discovery of Transforming Principle
● frederick griffith
● S. pneumoniae infects mice ⇒ pneumonia
● bacteria;
1. R bacterium
a. rough coat
b. no inflammation
2. S bacterium
, a. smooth coat
b. inflammation
● coat = virulence
1. R strain on mice ⇒ healthy
2. S strain on mice ⇒ dies
3. heat killed S ⇒ healthy
4. R + heat killed S ⇒ dies
a. in blood; live S strain S found
What is Transforming Principle?
● heat killed S transformed R bacteria to a new form that caused the disease
● when we add protease mouse dies
○ killed protein, nothing changed
● but if we add DNase it lives
○ killed DNA so no transform of genetic material
● conclusion: DNA is transforming principle
○ allow R bacteria to make S coat ⇒ infection
Hershey & Chase Bacterio-Phages
● viruses
○ protein + DNA
● infect bacteria
● inject heredity into bacteria
1. 35S virus injects DNA into bacteria (on the virus) ⇒ 35S remains outside
2. 32P (inside virus, DNA) injects DNA into bacteria ⇒ 35P remains inside
RNA Function as Genetic Material - Viruses
● isolated RNA from TMV (tobacco mosaic virus), plant virus
● purified RNA caused same injury as TMV
○ therefore; viral genome is composed of RNA
● not all viruses have DNA genome
Structure of Hereditary Material: Nucleotides in DNA
1. 2 deoxyribose (5C sugar)
2. phosphate
3. nitrogen base
a. adenine
b. guanine
c. thymine
d. cytosine
DNA (deoxyribonucleic acid) & RNA (ribonucleic acid) are Chains of Nucleotides
● nucleotides;
1. sugar
a. deoxyribose (DNA)
b. ribose (RNA)
, 2. phosphate
3. base
a. A, T (DNA)/U (RNA)
b. G, C
● RNA has extra OH on sugar (ribose)
● DNA has H for sugar (deoxyribose)
○ besides that (and bases) structure is same
1. base + sugar = nucleoside
a. adenine + ribose = adenosine
b. adenine + deox. = deoxyadenosine
2. base + sugar + phosphate = nucleotide
a. AMP = adenosine monophosphate
b. ADP = adenosine diphosphate
c. ATP = adenosine triphosphate
● base attached at 1’
● phosphate attached at 5’ end
Chargaff’s Experiment - Composition of DNA: The Data
● % adenine = % thymine
● % guanine = % cytosine
● complementary base pairs
○ A ⇒ T/U
■ 2H bonds
○ C⇒G
■ 3H bonds
Structure of DNA
● known from proteins
○ hemoglobin: a helix
, Rosalind Franklin - Key Experiment
● x ray
● studied wet DNA fibers
Model of DNA Structure
● James Watson
● Francis Crick
DNA Double Helix
● two DNA strands form right handed double helix
● 2 strands antiparallel ⇒ 5’ to 3’
○ 5 phosphate - 3 hydroxyl
● 10 nucleotides in each strands per complete 360 degree turn of helix
● phosphate and sugar ⇒ phosphodiester bond
● major groove; backbones are far
● minor groove; closer
Watson - Crick Model
● DNA; 2 nucleotide strands
○ connected by phosphodiester bond (DNA backbone)
● phosphate connects 5’C to 3’C
○ strands has directionality/polarity (5’ to 3’)
● phosphate + sugar = backbone of nucleic acid strand
● antiparallel
● strands held together by H bonds between bases
● base stacking ⇒ stability of double helix
DNA’s Alternative Types of Double Helices
● different types of secondary structure
○ B DNA; pre-dom. & right handed
○ A DNA & Z DNA
● bases are tilted or perpendicular to central axis
● sugar-phosphate backbone ⇒ zigzag pattern
1. A DNA
a. right handed
b. 11 bp per turn
c. low humidity
2. Z DNA
a. left handed
b. 12 bp per turn
c. CG rich at high salt concen.
d. C methylation at low salt concen.
e. transcripcion and recombination
Structures at Chromosome Ends (Telomeres)
1. G-quadruplex DNA
a. straight
CHAPTER 9
DNA’s role in medical science
● genetic disease
○ gene regulation
● cancer
● diagnostics
● genetic therapies
○ based on DNA/RNA
● DNA damage/damaging agents
● research
○ gene expression and modification
Roles of the Genetic Material
● Francis Crick
● genetic material has two jobs
○ duplicate
○ development control
Genetic Material Criteria
1. information
a. to make organism
2. transmission
a. parent to offspring
3. replication
a. copy
i. to pass from cell to cell
4. variation
a. changing
i. phenotypic variation
ii. adaptation and evolution
Friedrich Miescher Discovered DNA
● called ‘nuclein’ ⇒ now DNA
Evidence of DNA Being Responsible for Inheritance - Transmitting Traits
1. bacterial pathogens
2. viruses
Discovery of Transforming Principle
● frederick griffith
● S. pneumoniae infects mice ⇒ pneumonia
● bacteria;
1. R bacterium
a. rough coat
b. no inflammation
2. S bacterium
, a. smooth coat
b. inflammation
● coat = virulence
1. R strain on mice ⇒ healthy
2. S strain on mice ⇒ dies
3. heat killed S ⇒ healthy
4. R + heat killed S ⇒ dies
a. in blood; live S strain S found
What is Transforming Principle?
● heat killed S transformed R bacteria to a new form that caused the disease
● when we add protease mouse dies
○ killed protein, nothing changed
● but if we add DNase it lives
○ killed DNA so no transform of genetic material
● conclusion: DNA is transforming principle
○ allow R bacteria to make S coat ⇒ infection
Hershey & Chase Bacterio-Phages
● viruses
○ protein + DNA
● infect bacteria
● inject heredity into bacteria
1. 35S virus injects DNA into bacteria (on the virus) ⇒ 35S remains outside
2. 32P (inside virus, DNA) injects DNA into bacteria ⇒ 35P remains inside
RNA Function as Genetic Material - Viruses
● isolated RNA from TMV (tobacco mosaic virus), plant virus
● purified RNA caused same injury as TMV
○ therefore; viral genome is composed of RNA
● not all viruses have DNA genome
Structure of Hereditary Material: Nucleotides in DNA
1. 2 deoxyribose (5C sugar)
2. phosphate
3. nitrogen base
a. adenine
b. guanine
c. thymine
d. cytosine
DNA (deoxyribonucleic acid) & RNA (ribonucleic acid) are Chains of Nucleotides
● nucleotides;
1. sugar
a. deoxyribose (DNA)
b. ribose (RNA)
, 2. phosphate
3. base
a. A, T (DNA)/U (RNA)
b. G, C
● RNA has extra OH on sugar (ribose)
● DNA has H for sugar (deoxyribose)
○ besides that (and bases) structure is same
1. base + sugar = nucleoside
a. adenine + ribose = adenosine
b. adenine + deox. = deoxyadenosine
2. base + sugar + phosphate = nucleotide
a. AMP = adenosine monophosphate
b. ADP = adenosine diphosphate
c. ATP = adenosine triphosphate
● base attached at 1’
● phosphate attached at 5’ end
Chargaff’s Experiment - Composition of DNA: The Data
● % adenine = % thymine
● % guanine = % cytosine
● complementary base pairs
○ A ⇒ T/U
■ 2H bonds
○ C⇒G
■ 3H bonds
Structure of DNA
● known from proteins
○ hemoglobin: a helix
, Rosalind Franklin - Key Experiment
● x ray
● studied wet DNA fibers
Model of DNA Structure
● James Watson
● Francis Crick
DNA Double Helix
● two DNA strands form right handed double helix
● 2 strands antiparallel ⇒ 5’ to 3’
○ 5 phosphate - 3 hydroxyl
● 10 nucleotides in each strands per complete 360 degree turn of helix
● phosphate and sugar ⇒ phosphodiester bond
● major groove; backbones are far
● minor groove; closer
Watson - Crick Model
● DNA; 2 nucleotide strands
○ connected by phosphodiester bond (DNA backbone)
● phosphate connects 5’C to 3’C
○ strands has directionality/polarity (5’ to 3’)
● phosphate + sugar = backbone of nucleic acid strand
● antiparallel
● strands held together by H bonds between bases
● base stacking ⇒ stability of double helix
DNA’s Alternative Types of Double Helices
● different types of secondary structure
○ B DNA; pre-dom. & right handed
○ A DNA & Z DNA
● bases are tilted or perpendicular to central axis
● sugar-phosphate backbone ⇒ zigzag pattern
1. A DNA
a. right handed
b. 11 bp per turn
c. low humidity
2. Z DNA
a. left handed
b. 12 bp per turn
c. CG rich at high salt concen.
d. C methylation at low salt concen.
e. transcripcion and recombination
Structures at Chromosome Ends (Telomeres)
1. G-quadruplex DNA
a. straight
