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Nucleic Acids (Chapter 26)

Composition of Nucleic Acids (26.2)
nucleic acids are polymers of nucleotides (called polynucleotides)
3 parts of a nucleotide
NH2
Phosphate group
Heterocyclic nitrogen base
N
O
O
P
O
CH2
N
O
O
OH
Monosaccharide (a sugar)
The Sugars
HO
CH2
OH
O
HO
CH2
OH
O
Oxygen missing
OH
OH
D-ribose (in RNA)
OH
H
2-Deoxy-D-ribose (in DNA)
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The Bases
Adenine
DNA, RNA
Guanine
DNA, RNA
NH2
Cytosine
DNA, RNA
NH2
O
N
N
N
HN
N
H
N
H2N
Thymine
DNA
N
H
O
O
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H3C
N
N
H
N
Uracil
RNA
NH
O
N
H
O
3
5
NH
6
2
N
H 1
O
Sugar connects here
pyrimidines
purines
Sugar + Base = Nucleoside
NH2
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Dehydration synthesis - loss of water
CH2
OH
O
OH
N
N
+
OH
Ribose
N
Adenine
9 N
4
6
N 1
2
O
4’
3’
N
3
5’
HO
CH2
N
H
5
8
NH2
HO
N
1’
2’
OH
Change names:
Adenosine
Guanosine
Thymidine
Cytidine
Uridine
OH
Adenosine (a nucleoside)
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Sugar + Base + Phosphate = Nucleotide
Building blocks of nucleic acids - monomers of DNA and RNA
named by adding 5’ monophosphate at the end of the nucleoside name.
Adenosine 5’ monophosphate, guanosine 5’ monophosphate, etc
NH2
N
NH2
N
N
O
N
O
CH2
O
OH
N
N
HO
P
N
O
CH2
O
OH
O
OH
Adenosine (a nucleoside)
N
OH
Adenosine 5’-monophosphate (a nucleotide)
Ribonucleotide vs. deoxyribonucleotide
NH2
N
O
O
P
O
N
NH2
N
N
O
O
O
CH2
OH
N
N
O
P
O
OH
Ribonucleotide - contains ribose
used for RNA
N
N
O
CH2
O
OH
deoxyribonucleotide - contains deoxyribose
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used for DNA
Draw and name the 4 Nucleotides in DNA
NH2
N
-O
N
N
O
P
O
OH
N
N
O
H
O
N
O
-O
P
O
OH
H
N
NH2
O
H
O-
H
NH
H
H
H
OH
H
H
NH2
O
N
HN
O
O
N
O
O
-O
P
O
O
O-
H
-O
P
O
O
H
OH
N
H
H
H
OH
H
H
H
OH
H
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
Structure of Nucleic Acid Chains (26.3)
nucleotides are linked together through phosphodiester linkages
bond between 3’ OH group of nucleotide and the phosphate of the next
Note:
O
-O
P
5’ end
5’
O
N
CH2
O
O
O-
-O
3’
OH
P
5’
O
CH2
O
P
O
O
O
5’
O
N
O-
+
-O
pg. 745 fig is
wrong - the P is
not dbl bond to
the 3’ O
CH2
3’
O
CH2
N
N
O
O-
O
Phosphodiester link
O-
P
3’ OH
OH
3’ end
A dinucleotide
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The phosphates and sugars form the DNA backbone
DNA sequences differ based on the order of the bases like protein sequence differs
based on the order of the side chains
A DNA sequence is read from the 5’ to the 3’ end
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Draw the full structure of the trinucleotide C-A-T and label the 5’ and 3’ ends.
Draw a box around each nucleotide.
NH2
N
O
O
-O
P
O
N
O
O-
H
H
OH
H
NH2
H
H
N
N
O
-O
P
N
O
O
OH
H
H
OH
H
O
H
HN
O
O
-O
N
P
O
N
O
O-
H
H
OH
H
H
H
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
Base Pairing in DNA (25.4)
Chargaff’s Rules - %A = %T, %G = %C
DNA consists of 2 polynucleotide strands non-covalently interacting
Strands wind around each other in a helical, screw-like fashion - called the double helix
Sugar-phosphate backbone is on outside, bases are on inside
resembles a spiral staircase
The hydrophobic effect holds the 2 strands of DNA together - NOT H-BONDS
H-bonds and ion-dipole interactions with cations and solvent add to stability
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Watson-Crick Base-Pairing
H-bonds are responsible for directing replication and transcription
base pairing is described as complementary. If T is on one strand, A is on the opposite.
2 H-bonds
3 H-bonds
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
Structure of duplex DNA
2 Chains run antiparallel
3 types of duplex DNA
1) B-DNA - right handed helix - most studied/common form in body
10 base pairs per turn
2) A-DNA - right handed helix - found in low salt conditions
11 base pairs per turn
3) Z-DNA - left-handed helix - found in nature - function unknown
occurs in high G/C areas
B-DNA
wide major groove in B-DNA and narrow minor groove
many proteins such as DNA polymerase, RNA polymerase
bind in the major groove
major
minor
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
Organization of DNA
Total number of base pairs in a human cell is 3 billion
Chromosome - molecule of DNA
In humans - 46 chromosomes - 23 pairs of chromosomes
horse - 64 chromosomes (32 pairs)
cat has 38 (19 pairs)
mosquito has 6 (3 pairs)
If you straighten out all the DNA in a cell and line up end to end, there is about 2 meters
of DNA in each cell
Gene - each chromosome is made up of thousands of genes - estimated there are
~40,000 genes - codes for a protein
genetic code (26.9) - sequence of the bases specifies the sequence of amino acids
in a protein codon - base triplet that codes for an amino acid
insert codon table
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
Replication of DNA (26.6)
DNA double helix partially unwinds
Bases are added based on the opposing strand as nucleoside triphosphates
DNA polymerase is the enzyme that copies DNA - it catalyzes the formation of the
phosphodiester bond between the 3’ OH and the 5’ phosphate on an incoming
nucleoside triphosphate
New DNA is synthesized from the 5’ to the 3’ direction
New strand growing
OH attacks P
Bond breaks releasing
a lot of energy
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Replication is semi-conservative
Each strand in the parent DNA
acts as a template for the synthesis
of a new DNA strand.
End up with 2 new identical DNA molecules
with one parent strand per new molecule
and one new strand per new molecule
DNA always made in
5’ to 3’ direction and strands
are always antiparellel
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
Transcription of DNA (26.8)
Transcription - synthesis of messenger RNA (mRNA) using DNA as a template
occurs in the nucleus, 1st step in protein synthesis
DNA section to be transcribed is unwound
only 1 strand of DNA is used as a template (template strand)
the mRNA produced is complementary to the template strand but
identical to the non-template DNA strand (called the informational strand)
(except U for T and sugar)
mRNA is produced from the 5’ to the 3’ end like in replication
purpose of mRNA is to carry genetic information from DNA to cytosol
Example: Write the DNA complement (template strand) and the mRNA strand
DNA strand (informational strand) 5’ ATG CCA GTA GGC CAC TTG TCA 3’
DNA strand (template strand)
3’ TAC GGT CAT CCG GTG AAC AGT 5’
mRNA
5’ AUG CCA GUA GGC CAC UUG UCA 3’
mRNA made is a complete copy from start to stop codon
not everything copied is used to make protein
Exons are in pink - expressed part of gene
intervening parts that do
not code for protein
This is the mRNA that is used to make
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protein

Translation of mRNA (26.10)
Translation - synthesis of protein based on mRNA sequence
mRNA leaves nucleus - translation occurs in the
cytoplasm on ribosomes
ribosome - scaffolding for translation - holds the mRNA, tRNA,
and enzymes in place composed of rRNA and protein
t-RNA - each codon has a t-RNA with the corresponding amino
acid covalently attached
anticodon is at base of t-RNA molecule and is complementary to codon
on mRNA - the is responsible for bringing the correct amino acid to the
ribosome to add to the protein chain.
F in yellow
aa binds here
anticodon
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Genetic Mutations

Point Mutations- a single base change
Normal DNA
ATG-GAC-TTC
Mutant DNA
ATG-CAC-TTC
Classified as:
transitions- flipping the base pair to complement DNA: G to C or A to T.
(purine  purine or pyrimidine  pyrimidine)
transversions- switching base pairs: G/C to A/T.
(purine  pyrimidine or vice versa)
Is the above mutation a transition or transversion?
Point mutations may or may not affect transcription:
Missense mutations- a change that specifies a different AA. Ex. GUU  GCU resultin
Base substitution leads to AA substitution.
May result in no phenotype, mild, or very serious consequences.
Refer to pg. 757 table mRNA codon assignments of base triplets.
Normal DNA
ATG-GGC-TTC
RNA
AUG–GGC–UUC
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Amino acid
_Met_ - _Gly_ - _Phe_
Nonsense mutations- a change that produces a stop codon resulting in a prematurely
shortened protein.
ex. CGA  UGA gives Arg  stop
-The effects are variable depending upon how much truncated protein is present and
required for its function.
Normal DNA
RNA
Amino acid
TTG-AAC-TAC
AAC-UUG-AUG
_Asn_ - _Leu_ - _Met_
Normal DNA
RNA
Amino acid
TTG-ATC-TAC
AAC-UAG-AUG
_Asn_ - _stop_ - _Met_
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Silent mutations
causes a change that specifies the same AA. Ex. GUU  GUC results in Val Val
How is that possible?
(a) Often true in 3rd position of a codon, especially transitions. The change doesn
Modify the codon to produce a different AA ( single- nucleotide polymorphism (SNP) specif
The same AA.
(b) May terminate protein synthesis by introducing a stop codon.
the genetic code is degenerate
result
Normal DNA
RNA
Amino acid
TTG-ATC-TAC
AAC-UAG-ATG
_Asn_ - _stop_ - _Met__
Normal DNA
RNA
Amino acid
TTG-A TT-TAC
AAC-UA A-ATG
_Asn_ - _stop_ - _Met_
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Frameshift mutations- the number of the inserted or deleted base
Not in a multiple of 3, so that all triplets following the mutation are
Read differently.

(a) this mutation changes all the AA downstream & very likely to create a
nonfunctional product since it may differ greatly from normal protein.
(b) reading frames other than the correct one often contain stop codons which
will truncate the mutant protein prematurely.
Deletion Mutation
* loss of one or more bases
Normal DNA
ATG-GAC-TTC
Mutant DNA
ATG – GCT- TC
Insertion Mutation
* addition of one or more bases
Normal DNA
ATG-GAC-TTC
Mutant DNA
ATT - GGA – CTT- C
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
Causes of Mutations
Can be the result of different events:
1) Spontaneous- occurs as a result of natural processes in the cell.
- naturally occurring mutagens in the environment
- DNA replication errors
2) Mutagens- external agent that can cause a mutation (induced)
- error in base sequence that is carried along in DNA replication.
Carcinogens – cancer causing agents/ chemicals in the
environment. ( contain polycyclic aromatic hydrocarbons and
amines)
Examples: lung cancer from chemicals in cigarettes
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
Sunbathing damages DNA
UV radiation does numerous things to DNA
1) Causes breaks in sugar phosphate backbone - DNA cannot replicate/transcribe
- results in cell death
2) Causes “photodimers” - thymine dimers are most common - occurs btw adj T on
same strand
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Thymine dimers “kink” DNA
Undamaged DNA
UV damaged DNA
thymine dimer pulls thymines
closer together causing the
DNA kink
The kink causes:
1) replication/transcription to terminate at the point of the dimer
or even worse,
2) DNA polymerase iota will replicate through but misinserts T or G opposite one 23
of the thymines in the dimer instead of A and only 1 base is inserted opposite it.

Cigarette smoke damages DNA
Benzo[a]pyrene is the main cancer causing agent in cigarette smoke
Benzo[a]pyrene enters body and is converted to BPDE which covalently attaches
to DNA
This is your DNA
This is your DNA on Cigarettes
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How does BPDE cause mutations?
p53 - tumor suppressor protein
- scans DNA for damage during cell division
- if damage is spotten, p53 stops cell division and activates DNA repair systems
- if damage is too severe to be fixed, p53 triggers apoptosis (programmed cell
death)
- over 50% of all cancers have a disabled p53
- over 80% of all lung cancers have a disabled p53
BDPE is a potent mutagen of p53 by causing
G:C to T:A transversions
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