The central dogma of

molecular biology.
Bacteriophages attached to
the surface of a bacterium.
P
a
g
e

8
4

FIGURE 17.10 The Hershey-Chase Experiment
The Hershey-Chase
experiment.
1952
Alfred Hershey and
Martha Chase
Diagram of T2 bacteriophage
injecting its DNA into an E. coli cell.
FIGURE 17.9 Fred Griffiths Experiment
WHAT IS DNA?
Scientists have studied how organisms organize and
process genetic information, revealing the following
principles:
1. DNA directs the function of living cells and is
transmitted to offspring
DNA is composed of two polydeoxynucleotide strands
forming a double helix
Figure 17.2 Two Models of
DNA Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
A gene is a DNA sequence that contains the base
sequence information to code for a gene product,
protein, or RNA
The complete DNA base sequence of an organism is its
genome
DNA synthesis, referred to as replication, involves
complementary base pairing between the parental and
newly synthesized strand
Figure 17.2 Two Models of
DNA Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
2. The synthesis of RNA
begins the process of decoding
genetic information
RNA synthesis is called
transcription and involves
complementary base pairing
of ribonucleotides to DNA
bases
Each new RNA is a
transcript
The total RNA transcripts
for an organism comprise its
transcriptome
Figure 17.3a An Overview of
Genetic Information Flow
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
3. Several RNA molecules
participate directly in the
synthesis of protein, or
translation
Messenger RNA (mRNA)
specifies the primary
protein sequence
Transfer RNA (tRNA)
delivers the specific amino
acid
Ribosomal RNA (rRNA)
molecules are components
of ribosomes
Figure 17.3b An Overview of
Genetic Information Flow
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
The proteome is the entire
set of proteins synthesized
4. Gene expression is the
process by which cells
control the timing of gene
product synthesis in
response to environmental
or developmental cues
Metabolome refers to the
sum total of low molecular
weight metabolites
produced by the cell
Figure 17.3b An Overview of
Genetic Information Flow
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
The Central dogma schematically summarizes the
previous information
Includes replication, transcription, and
translation
The central dogma is generally how the flow of
information works in all organisms, except some
viruses have RNA genomes and use reverse
transcriptase to make DNA (e.g., HIV)
Section 17.1: DNA
DNA RNA Protein
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
DNA consists of two
polydeoxynucleotide strands
that wind around each other
to form a right-handed
double helix

Each DNA nucleotide
monomer is composed of
a nitrogenous base, a
deoxyribose sugar, and
phosphate
Figure 17.4 One
strand of DNA
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Nucleotides are linked
by 3,5-phosphodiester
bonds
These join the 3-
hydroxyl of one
nucleotide to the 5-
phosphate of another
Figure 17.4 DNA Strand Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
5
3
5
3
FIGURE 17.11 X-Ray Diffraction Study of DNA by Rosalind Franklin and R. Gosling
Two strands of DNA are oriented in opposite
orientations they are antiparallel.
The antiparallel nature of the two strands allows
hydrogen bonds to form between the nitrogenous
bases

Two types of base pair (bp) in DNA: (1) adenine
(purine) pairs with thymine (pyrimidine) and (2) the
purine guanine pairs with the pyrimidine cytosine
Figure 17.5 DNA Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
3
5
5
3
Oxygen is missing in 2deoxyribose
Page 40
Page 40
The dimensions of
crystalline B-DNA
have been precisely
measured:
1. One turn of the
double helix spans
3.32 nm and
consists of 10.3
base pairs
Figure 17.6 DNA Structure:
GC Base Pair Dimensions
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
2. Diameter of the double
helix is 2.37 nm, only
suitable for base pairing a
purine with a pyrimidine
3. The distance between
adjacent base pairs is
0.29-0.30 nm
Figure 17.6 DNA Structure:
AT Base Pair Dimensions
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
DNA is a relatively stable molecule with several noncovalent
interactions adding to its stability
1. Hydrophobic interactionsinternal base clustering
2. Hydrogen bondsformation of preferred bonds: three
between CG base pairs and two between AT base pairs
3. Base stackingbases are nearly planar and stacked,
allowing for weak van der Waals forces between the rings
4. Hydrationwater interacts with the structure of DNA
to stabilize structure
5. Electrostatic interactionsdestabilization by
negatively charged phosphates of sugar-phosphate
backbone are minimized by the shielding effect of water
on Mg
2+
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Tautomerism of nucleobases
Prototropic tautomers are structural isomers that
differ in the location of protons
Keto-enol tautomerism is common in ketones
Lactam-lactim tautomerism occurs in some
heterocycles
Both tautomers exist in solution but the lactam
forms are predominant at neutral pH

FIGURE 17.7 A Tautomeric Shift Causes a Transition Mutation
DNA Structure: The Nature of Mutation
DNA is eminently suited for information storage but
not static
Despite its stability, it is vulnerable to certain
disruptive forces that can cause mutations
Most negative or neutral rare positive mutations can
enhance the adaptation of the organism
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Mutation typesThe most common are small single
base changes, also called point mutations
This results in transition or transversion
mutations
Transition mutations, caused by deamination, lead to
purine for purine or pyrimidine for pyrimidine
substitutions
Transversion mutations, caused by alkylating agents
or ionizing radiation, occur when a purine is
substituted for a pyrimidine or vice versa
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Point mutations that occur in a population with any
frequency are referred to as single nucleotide
polymorphisms (SNPs)
Point mutations that occur within the coding portion
of a gene can be classified according to their impact on
structure and/or function:
Silent mutations have no discernable effect
Missense mutations have an observable effect
Nonsense mutations changes a codon for an amino
acid to that of a premature stop codon
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Insertions and deletions, or indels, occur from one to
thousands of bases
Indels that occur within the coding region that are
not divisible by three cause a frameshift mutation
Genome rearrangements can cause disruptions in
gene structure or regulation.
Occur as a result of double strand breaks and can
lead to inversions, translocations, or duplications
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Inversions result when deleted DNA is reinserted into
its original position in the opposite orientation
Translocation is when a DNA fragment inserts else
where in the genome
Duplication is the creation of duplicate genes or parts
of genes.
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Causes of DNA DamageDNA damage can result
from exogenous and endogenous forces
Endogenous sources can include tautomeric shifts,
depurination, deamination, and ROS-induced oxidative
damage
Exogenous factors such as radiation and xenobiotic
exposure can also be mutagenic
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Tautomeric shifts are spontaneous changes to
nucleotide base structure
Amino to imino groups and keto to enol groups
If tautomers form during replication, base
mispairings can occur
The imino form of adenine does not pair with
thymine; it pairs with cytosine
Several spontaneous hydrolytic reactions can cause
DNA damage
Depurination or deamination is also possible, which
could cause a mutation in the next round of replication
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Figure 17.7 A Tautomeric Shift
Causes a Transition Mutation
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Ionizing radiation (e.g., UV and X-rays) can alter
DNA structure
Radiation-induced damage via free radical
mechanisms can cause strand breaks, DNA-protein
cross linking, ring openings, and base modifications
The most common UV-induced products are thymine-
thymine dimers
Figure 17.8 Thymine
Dimer Structure
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Xenobiotics can damage DNA; classes include:
Base analogues have structures so similar to bases
they can be incorporated into DNA
Alkylating agents cause alkylation, which is the
electrophilic attack on molecules with unpaired
electrons
Often add carbon-containing alkyl groups
Often base pair incorrectly, leading to
transition or transversion mutations

Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Nonalkylating agentsa variety of other
chemicals can modify DNA structure
For example, nitrous acid and sodium nitrite
can deaminate bases
Intercalating agents are planar polycyclic
aromatic molecules that can distort DNA by
inserting themselves between the stacked bases
Causes base pair deletion or insertion
The intercalating agent ethidium bromide is a
fluorescent tag molecule used as a nucleic acid
stain
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
DNA Structure: The Genetic Material
In the early decades of the twentieth century, life
scientists believed that of the two chromosome
components (DNA and protein) that protein was most
likely responsible for transmission of inherited traits
The work of several scientists would lead to another
conclusion

Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
In 1928, Fred Griffith
performed a remarkable set
of experiments involving
pneumococcal strains:
smooth (S) and rough (R)
Identified the concept of
transformation, though few
accepted his discovery
Figure 17.9 Fred Griffiths
Experiment
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
In 1944, Oswald Avery and colleagues reported the
identification of Griffiths transforming principle as
DNA
Everyone was still not convinced
It was not until 1952, when Hershey and Chase
demonstrated the different functions of protein and
DNA with their T2 bacteriophage experiment, that
DNA was accepted as the genetic material
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
The Hershey-Chase experiment confirmed DNA as
the transforming principle
Figure 17.10 The
Hershey-Chase
Experiment
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Determining the structure of
DNA became an obvious priority
Investigators including Linus
Pauling, Maurice Wilkins,
Rosalind Franklin, James
Watson, and Francis Crick all
worked toward this goal
Watson and Crick won the race
for the double helix and
published their findings in the
journal Nature in 1953
They were awarded the Nobel
Prize in chemistry in 1962
Section 17.1: DNA
Figure 17.1 The First Complete
Structural Model of DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
Information used to construct
the model of DNA:
1. Chemical and physical
dimensions of deoxyribose,
nitrogenous bases, and
phosphate
2. 1:1 Ratios of adenine to
thymine and cytosine to guanine
(Chargaff s rules)
3. X-ray diffraction studies of
Rosalind Franklin
Figure 17.11 X-Ray Diffraction
Study of DNA by Rosalind
Franklin and R. Gosling
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press
4. Wilkins and Stokes diameter and
pitch estimates from X-ray
diffraction
5. Linus Paulings recent
demonstration that proteins could
exist in a helical conformation
Figure 17.12 X-Ray Diffraction
Study of DNA by Rosalind
Franklin and R. Gosling
Section 17.1: DNA
From McKee and McKee, Biochemistry, 5th Edition, 2011 Oxford University Press