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ACIDS
Topic Outline:
History of Nucleic Acids
Structure and Function
Types of Nucleic Acids
1. DNA
2. RNA
Central Dogma of Life
Friedrich Miescher in
1869
isolated what he called nuclein from the
nuclei of pus cells
Richard Altmann in 1889
pentose
pentose
phosphate
phosphate
pentose pentose
RNA
ribonucleic acid
3 types of RNA in a cell
Ribosomal RNAs (rRNA) are components of ribosomes
Messenger RNAs (mRNA) carry genetic information
Transfer RNAs (tRNA) are adapter molecules in translation
The distribution of nucleic
acids in the eukaryotic
DNA is found in the nucleus
cell
with small amounts in mitochondria and
chloroplasts
RNA is found throughout the cell
The nucleus contains the cell’s DNA
(genome)
Nucleus
RNA is synthesized in the nucleus
and
exported to the cytoplasm
Nucleus
Cytoplasm
DNA as genetic material:
The circumstantial evidence
1. Present in all cells and virtually restricted to the nucleus
2. The amount of DNA in somatic cells (body cells) of any
given species is constant (like the number of
chromosomes)
3. The DNA content of gametes (sex cells) is half that of
somatic cells.
In cases of polyploidy (multiple sets of chromosomes)
the DNA content increases by a proportional factor
4. The mutagenic effect of UV light peaks at 253.7nm. The
peak for the absorption of UV light by DNA
NUCLEIC ACID STRUCTURE
NUCLEOTIDE
Nucleotide Structure
All nucleotides contain three components:
1. A nitrogen heterocyclic base
2. A pentose sugar
3. A phosphate residue
Ribose is a pentose
C5
C4 C1
C3 C2
Spot the difference
RIBOSE DEOXYRIBOSE
CH2OH CH2OH
O OH O OH
C C C C
H H H H H H H H
C C C C
OH OH OH H
Chemical Structure of DNA vs RNA
Ribonucleotides have a 2’-OH
Deoxyribonucleotides have a 2’-H
P
THE SUGAR-PHOSPHATE
BACKBONE P
direction
The phosphate group joins the P
P
P
G
DNA IS MADE OF P
G
TWO STRANDS OF C
P
POLYNUCLEOTIDE P
C G
P
P
C G
P
P
A T
P
P
T A
P
P
T A
P
DNA IS MADE OF TWO STRANDS OF
POLYNUCLEOTIDE
The sister strands of the DNA molecule run in opposite
directions (antiparallel)
They are joined by the bases
Each base is paired with a specific partner:
A is always paired with T
G is always paired with C
“Purine with Pyrimidine”
The sister strands are complementary but not identical
The bases are joined by hydrogen bonds, individually
weak but collectively strong
There are 10 base pairs per turn
Purines & Pyrimidines
Structure of Nucleotide
Bases
5’ End
Nucleotides
are
linked by
phosphodies
ter
bonds
3’ End
From DNA to Protein
DNA to Protein
DNA acts as a “manager” in the process of
making proteins
DNA is the template or starting sequence
that is copied into RNA that is then used
to make the protein
Central Dogma
Original theory
Begin adding nucleotides at origin
Add subsequent bases following pairing rules
Expect both strands to be synthesized simultaneously
This is NOT how it is accomplished
How is DNA Synthesized?
Actually how DNA is synthesized
Simple addition of nucleotides along one strand, as
expected
Called the leading strand
DNA polymerase reads 3’ 5’ along the leading
strand from the RNA primer
Synthesis proceeds 5’ 3’ with respect to the new
daughter strand
Remember how the nucleotides are added!!!!!
5’ 3’
Mistakes during
Replication
Base pairing rules must be maintained
Mistake = genome mutation, may have consequence
on daughter cells
Only correct pairings fit in the polymerase active
site
If wrong nucleotide is included
Polymerase uses its proofreading ability to cleave the
phosphodiester bond of improper nucleotide
Activity 3’ 5’
And then adds correct nucleotide and proceeds down
the chain again in the 5’ 3’ direction
Proofreading
DNA Repair
1. Induced
viruses, UV radiation, some chemicals
(nitric acid changes cytosine to uracil) or
mutagens (or carcinogens - benzene,
cigarette smoke).
Types of Mutation
2. Spontaneous
Proofreading mistakes during DNA replication
(Base substitutions) - not necessarily a serious
change.
Deletions
THE CAT SAW TED OG
THE ATS AWT HED OG
Additions
THE CAT SAW THE ZDO G
THE CMA TAS WTH EDO G
Types of Mutation
5. Homeotic genes
master genes that regulate suites of other genes and
may affect developmental pathways especially during
embryogenesis. Mutations in these master genes can
cause genetic anomalies. For example, a fruit fly that
possesses legs where antennae should be, or a
mosquito that has its mouth parts transformed into
legs.
Effect of Mutation
Uncorrected Replication
Errors
Mismatch repair
Enzyme complex recognizes mistake and excises newly-
synthesized strand and fills in the correct pairing
Mismatch Repair – cont’d
Eukaryotes “label”
the daughter strand
with nicks to
recognize the new
strand
Separates new from
old
Chemical Modifications
Thymine Dimers
Reads template 3’
to 5’
Adds nucleotides
5’ to 3’ (5’
phosphate to 3’
hydroxyl)
Synthesis is the
same as the
leading strand of
DNA
Differences in
DNA and RNA Polymerases
RNA polymerase adds ribonucleotides not
deoxynucleotides
RNA polymerase does not have the ability to
proofread what they transcribe
RNA polymerase can work without a primer
RNA will have an error 1 in every 10,000
nucleotides (DNA is 1 in 100,000,000 nucleotides)
Types of RNA
2
1
Ribosomes Complex machinery that
controls protein synthesis
2 subunits
1 large – catalyzes the peptide
bond formation
1 small – binds mRNA and tRNA
Contains protein and RNA
rRNA central to the catalytic
activity
Folded structure is highly conserved
Protein has less homology and
may not be as important
Ribosome Structures
E-site
4 binding sites
mRNA binding site
Peptidyl-tRNA binding site (P-site)
Holds tRNA attached to growing end of the peptide
Aminoacyl-tRNA binding site (A-site)
Holds the incoming AA
Exit site (E-site)
Summary