1B Nucleotides—Joining a Nucleoside with a Phosphate
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NUCLEOSIDES AND NUCLEOTIDES
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TABLE 22.1
Base
Names of Bases, Nucleosides, and Nucleotides
in Nucleic Acids
Abbreviation
Nucleoside
Nucleotide
Abbreviation
DNA
Adenine
A
Deoxyadenosine
Deoxyadenosine 5'-monophosphate
dAMP
Guanine
G
Deoxyguanosine
Deoxyguanosine 5'-monophosphate
dGMP
Cytosine
C
Deoxycytidine
Deoxycytidine 5'-monophosphate
dCMP
Thymine
T
Deoxythymidine
Deoxythymidine 5'-monophosphate
dTMP
Adenine
A
Adenosine
Adenosine 5'-monophosphate
AMP
Guanine
G
Guanosine
Guanosine 5'-monophosphate
GMP
Cytosine
C
Cytidine
Cytidine 5'-monophosphate
CMP
Uracil
U
Uridine
Uridine 5'-monophosphate
UMP
RNA
Di- and triphosphates can also be prepared from nucleosides by adding two and three phosphate groups, respectively, to the 5'-OH. For example, adenosine can be converted to adenosine
5'-diphosphate and adenosine 5'-triphosphate, abbreviated as ADP and ATP, respectively. We
will learn about the central role of these phosphates, especially ATP, in energy production in
Chapter 23.
NH2
O
−O
P
O−
N
O
O
P
O
5'
CH2
N
O
NH2
N
N
O
−O
O−
P
O
O
O−
OH
P
O
O−
O
P
CH2
N
O
N
N
O−
OH
OH
adenosine 5'-diphosphate
ADP
SAMPLE PROBLEM 22.2
N
O
OH
adenosine 5'-triphosphate
ATP
Draw the structure of the nucleotide GMP.
ANALYSIS
Translate the abbreviation to a name; GMP is guanosine 5'-monophosphate. First, draw the
sugar. Since there is no deoxy prefix in the name, GMP is a ribonucleotide and the sugar is
ribose. Then draw the base, in this case guanine, bonded to C1' of the sugar ring. Finally, add
the phosphate. GMP has one phosphate group bonded to the 5'-OH of the nucleoside.
SOLUTION
Add phosphate here.
HO
O
Add base here.
CH2
O
N
O
OH
−O
P
O
5'
CH2
N
O
1'
O−
OH
NH
N
NH2
OH
OH
OH
ribose
guanosine 5'-monophosphate
GMP
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NUCLEIC ACIDS AND PROTEIN SYNTHESIS
PROBLEM 22.3
Draw the structure of each nucleotide: (a) UMP; (b) dTMP; (c) AMP.
PROBLEM 22.4
Give the name that corresponds to each abbreviation: (a) GTP; (b) dCDP; (c) dTTP; (d) UDP.
PROBLEM 22.5
Draw the structure of dCTP.
22.2 NUCLEIC ACIDS
Nucleic acids—both DNA and RNA—are polymers of nucleotides, formed by joining the
3'-OH group of one nucleotide with the 5'-phosphate of a second nucleotide in a phosphodiester linkage (Section 19.6).
O
R
P
O
O
R
O−
phosphodiester
For example, joining the 3'-OH group of dCMP (deoxycytidine 5'-monophosphate) and the
5'-phosphate of dAMP (deoxyadenosine 5'-monophosphate) forms a dinucleotide that contains
a 5'-phosphate on one end (called the 5' end) and a 3'-OH group on the other end (called the
3' end).
NH2
N
O
−O
P
O
5'
CH2
N
O
A dinucleotide
NH2
O
5'-phosphate
O−
dCMP
+
−O
P
O
−O
NH2
N
O
O
5'
CH2
O
N
P
O
5'
CH2
N
dAMP
N
O
O
NH2
O−
3'
O
N
−
3'
OH
N
O
3'
OH
phosphodiester
linkage
O
P
N
O
5'
CH2
O
N
N
N
O−
3'
OH
3'-OH
As additional nucleotides are added, the nucleic acid grows, each time forming a new phosphodiester linkage that holds the nucleotides together. Figure 22.2 illustrates the structure of a polynucleotide formed from four different nucleotides. Several features are noteworthy.
• A polynucleotide contains a backbone consisting of alternating sugar and phosphate
groups. All polynucleotides contain the same sugar–phosphate backbone.
• The identity and order of the bases distinguish one polynucleotide from another.
• A polynucleotide has one free phosphate group at the 5' end.
• A polynucleotide has a free OH group at the 3' end.
The primary structure of a polynucleotide is the sequence of nucleotides that it contains. This
sequence, which is determined by the identity of the bases, is unique to a nucleic acid. In DNA,
the sequence of bases carries the genetic information of the organism.
Polynucleotides are named by the sequence of the bases they contain, beginning at the 5' end and
using the one-letter abbreviation for the bases. Thus, the polynucleotide in Figure 22.2 contains
the bases cytosine, adenine, thymine, and guanine, in order from the 5' end; thus, it is named
CATG.
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NUCLEIC ACIDS
▼
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FIGURE 22.2
Primary Structure of a Polynucleotide
5'-phosphate
sugar–phosphate backbone
O
−O
P
5'
CH2
O
cytosine
5'-phosphate P
O
O−
O
C
3'
O
O
P
P
5'
CH2
O
adenine
O
A
O
O−
=
3'
P
O
O
O
P
O
5'
CH2
T
thymine
O
O−
P
3'
O
G
O
P
O
The phosphodiester linkage joins
the 3' C of one nucleotide to the
5' C of another nucleotide.
O
5'
CH2
O−
guanine
O
3'-OH
HO
3'
OH
3'-OH
In a polynucleotide, phosphodiester bonds join the 3'-carbon of one nucleotide to the 5'-carbon of another. The name of a
polynucleotide is read from the 5' end to the 3' end, using the one-letter abbreviations for the bases it contains. Drawn is the
structure of the polynucleotide CATG.
SAMPLE PROBLEM 22.3
(a) Draw the structure of a dinucleotide formed by joining the 3'-OH group of AMP to the
5'-phosphate in GMP. (b) Label the 5' and 3' ends. (c) Name the dinucleotide.
ANALYSIS
Draw the structure of each nucleotide, including the sugar, the phosphate bonded to C5', and the
base at C1'. In this case the sugar is ribose since the names of the mononucleotides do not contain
the prefix deoxy. Bond the 3'-OH group to the 5'-phosphate to form the phosphodiester bond. The
name of the dinucleotide begins with the nucleotide that contains the free phosphate at the 5' end.
SOLUTION
a. and b.
NH2
NH2
N
O
−O
P
O
5'
CH2
N
−O
O
OH
P
O
O
O
O
N
5'
CH2
N
OH
P
O
OH
5'
CH2
N
O
N
3'
OH
N
NH2
adenine
A
N
O−
NH
O−
OH
N
O
3'
O
+
O
N
O
AMP
OH
Form a phosphodiester
using the 3'-OH and
5'-phosphate.
P
5'
CH2
O−
O−
3'
N
O
−O
N
O
5'-phosphate
N
OH
NH
N
NH2
guanine
G
3'-OH
GMP
c. Since polynucleotides are named beginning at the 5' end, this dinucleotide is named AG.
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NUCLEIC ACIDS AND PROTEIN SYNTHESIS
PROBLEM 22.6
Draw the structure of a dinucleotide formed by joining the 3'-OH group of dTMP to the
5'-phosphate in dGMP.
PROBLEM 22.7
Draw the structure of each polynucleotide: (a) CU; (b) TAG.
PROBLEM 22.8
Label the 5' end and the 3' end in each polynucleotide: (a) ATTTG; (b) CGCGUU; (c) GGACTT.
22.3 THE DNA DOUBLE HELIX
Our current understanding of the structure of DNA is based on the model proposed initially by
James Watson and Francis Crick in 1953 (Figure 22.3).
• DNA consists of two polynucleotide strands that wind into a right-handed double helix.
The sugar–phosphate backbone lies on the outside of the helix and the bases lie on the inside,
perpendicular to the axis of the helix. The two strands of DNA run in opposite directions; that is,
one strand runs from the 5' end to the 3' end, while the other runs from the 3' end to the 5' end.
▼
FIGURE 22.3 The Three-Dimensional Structure of DNA—A Double Helix
a.
b.
sugar–phosphate
backbone
bases
G
C
T
A
bases
DNA consists of a double helix of polynucleotide chains. In view (a), the three-dimensional
molecular model shows the sugar–phosphate backbone with the red (O), black (C), and white
(H) atoms visible on the outside of the helix. In view (b), the bases on the interior of the helix
are labeled.
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THE DNA DOUBLE HELIX
691
▼
FIGURE 22.4 Hydrogen Bonding in the DNA Double Helix
5'
3'
H
O
H
N
H
N
H
N
N
N
N
N
G
C
C
H
A
H
CH3
O
N
H
N
N
N
T–A base pair
H
N
N
3'
5'
G–C base pair
O
G
T
N
T
N
A
O
hydrogen bonding between base pairs
Hydrogen bonding of base pairs (A–T and C–G) holds the two strands of DNA together.
The double helix is stabilized by hydrogen bonding between the bases of the two DNA strands
as shown in Figure 22.4. A purine base on one strand always hydrogen bonds with a pyrimidine
base on the other strand. Two bases hydrogen bond together in a predictable manner, forming
complementary base pairs.
• Adenine pairs with thymine using two hydrogen bonds, forming an A–T base pair.
• Cytosine pairs with guanine using three hydrogen bonds, forming a C–G base pair.
Because of this consistent pairing of bases, knowing the sequence of one strand of DNA allows
us to write the sequence of the other strand, as shown in Sample Problem 22.4.
SAMPLE PROBLEM 22.4
ANALYSIS
Write the sequence of the complementary strand of the following portion of a DNA molecule:
5'–TAGGCTA–3'.
The complementary strand runs in the opposite direction, from the 3' to the 5' end. Use base
pairing to determine the corresponding sequence on the complementary strand: A pairs with T
and C pairs with G.
SOLUTION
Original strand: 5'–T A G G C T A–3'
Complementary strand: 3'–A T C C G A T–5'
PROBLEM 22.9
Write the complementary strand for each of the following strands of DNA.
a. 5'–AAACGTCC–3'
b. 5'–TATACGCC–3'
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c. 5'–ATTGCACCCGC–3'
d. 5'–CACTTGATCGG–3'
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NUCLEIC ACIDS AND PROTEIN SYNTHESIS
692
The enormously large DNA molecules that compose the human genome—the total DNA content
of an individual—pack tightly into the nucleus of the cell. The double-stranded DNA helices
wind around a core of protein molecules called histones to form a chain of nucleosomes, as
shown in Figure 22.5. The chain of nucleosomes winds into a supercoiled fiber called chromatin,
which composes each of the 23 pairs of chromosomes in humans.
In Section 22.2 we learned that the genetic information of an organism is stored in the
sequence of bases of its DNA molecules. How is this information transferred from one generation to another? How, too, is the information stored in DNA molecules used to direct the synthesis of proteins?
▼
FIGURE 22.5 The Structure of a Chromosome
chromosome
nucleus
chromatin fiber
cell
nucleosome
histones
DNA (double helix)
base pairs
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REPLICATION
693
To answer these questions we must understand three key processes.
• Replication is the process by which DNA makes a copy of itself when a cell divides.
• Transcription is the ordered synthesis of RNA from DNA. In this process, the genetic
information stored in DNA is passed onto RNA.
• Translation is the synthesis of proteins from RNA. In this process, the genetic message
contained in RNA determines the specific amino acid sequence of a protein.
parent
DNA
transcription
translation
RNA
protein
replication
daughter
DNA
Each chromosome contains many genes, those portions of the DNA molecules that result in the
synthesis of specific proteins. We say that the genetic message of the DNA molecule is expressed
in the protein. Only a small fraction (1–2%) of the DNA in a chromosome contains genetic messages or genes that result in protein synthesis.
22.4 REPLICATION
How is the genetic information in the DNA of a parent cell passed onto new daughter cells during
replication? The structure of the double helix and the presence of complementary base pairs are
central to the replication process.
During replication, the strands of DNA separate and each serves as a template for a new strand.
Thus, the original DNA molecule forms two DNA molecules, each of which contains one
strand from the parent DNA and one new strand. This process is called semiconservative
replication. The sequence of both strands of the daughter DNA molecules exactly matches the
sequence in the parent DNA.
parent DNA
5'
A
T
T
A
T
A
C
G
G
C
A
T
1
2
daughter DNA
5'
3'
3'
replication
3'
5'
3'
5'
daughter DNA
5'
A
T
T
3'
A
T
A
T
A
T
A
T
A
C
G
C
G
G
C
G
C
A
T
A
T
1
2
1
2
+
3'
5'
strand
new strand
new strand
Although the semiconservative nature of replication has been known since the elegant experiments of Matthew Meselson and Franklin Stahl were reported in 1958, the details of replication have only slowly been determined over the last 50 years. The first step in replication is the
unwinding of the DNA helix to expose the bases on each strand. Unwinding occurs at many
places simultaneously along the helix, creating “bubbles” where replication can occur. The point
at which unwinding occurs is called the replication fork. Unwinding breaks the hydrogen bonds
that hold the two strands of the double helix together.
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NUCLEIC ACIDS AND PROTEIN SYNTHESIS
Once bases have been exposed on the unwound strands of DNA, the enzyme DNA polymerase
catalyzes the replication process using the four nucleoside triphosphates (derived from the bases
A, T, G, and C) that are available in the nucleus. Three features are key and each is illustrated in
Figure 22.6.
▼
FIGURE 22.6 DNA Replication
thymine
adenine
cytosine
guanine
replication fork
template strand
template strand
The lagging strand
replicates in segments.
DNA polymerase
nucleoside
triphosphate
5'
Replication proceeds
in the 3'-to-5' direction
of the template for
both the leading and
the lagging strands.
5'
3'
The leading strand
grows continuously.
Replication proceeds along both strands of unwound DNA. Replication always occurs in the
same direction, from the 3' to the 5' end of the template strand. The leading strand grows
continuously, while the lagging strand must be synthesized in fragments that are joined
together by a DNA ligase enzyme.
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RNA
695
• The identity of the bases on the template strand determines the order of the bases on
the new strand: A must pair with T, and G must pair with C.
• A new phosphodiester bond is formed between the 5'-phosphate of the nucleoside
triphosphate and the 3'-OH group of the new DNA strand.
• Replication occurs in only one direction on the template strand, from the 3' end to the
5' end.
Since replication proceeds in only one direction—that is, from the 3' end to the 5' end of the
template—the two new strands of DNA must be synthesized by somewhat different techniques.
One strand, called the leading strand, grows continuously. Since its sequence is complementary
to the template, its nucleotide sequence grows in the 5' to 3' direction. The other strand, called
the lagging strand, is synthesized in small fragments, which are then joined together by a DNA
ligase enzyme. The end result is two new strands of DNA, one in each of the daughter DNA molecules, both with complementary base pairs joining the two DNA strands together.
SAMPLE PROBLEM 22.5
ANALYSIS
What is the sequence of a newly synthesized DNA segment if the template strand has the
sequence 3'–TGCACC–5'?
The newly synthesized strand runs in the opposite direction, from the 5' end to the 3' end in this
example. Use base pairing to determine the corresponding sequence on the new strand: A pairs
with T and C pairs with G.
SOLUTION
Template strand: 3'–T G C A C C–5'
New strand: 5'–A C G T G G–3'
PROBLEM 22.10
What is the sequence of a newly synthesized DNA segment if the template strand has each of
the following sequences?
a. 3'–AGAGTCTC–5'
b. 5'–ATTGCTC–3'
c. 3'–ATCCTGTAC–5'
d. 5'–GGCCATACTC–3'
22.5 RNA
While RNA is also composed of nucleotides, there are important differences between DNA and
RNA. In RNA,
• The sugar is ribose.
• U (uracil) replaces T (thymine) as one of the bases.
• RNA is single stranded.
RNA molecules are much smaller than DNA molecules. Although RNA contains a single strand,
the chain can fold back on itself, forming loops, and intermolecular hydrogen bonding between
paired bases on a single strand can form helical regions. When base pairing occurs within an RNA
molecule (or between RNA and DNA), C and G form base pairs, and A and U form base pairs.
There are three different types of RNA molecules.
• Ribosomal RNA (rRNA)
• Messenger RNA (mRNA)
• Transfer RNA (tRNA)
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NUCLEIC ACIDS AND PROTEIN SYNTHESIS
Ribosomal RNA, the most abundant type of RNA, is found in the ribosomes in the cytoplasm of the
cell. Each ribosome is composed of one large subunit and one small subunit that contain both RNA
and protein. rRNA provides the site where polypeptides are assembled during protein synthesis.
Messenger RNA is the carrier of information from DNA (in the cell nucleus) to the ribosomes
(in the cytoplasm). Each gene of a DNA molecule corresponds to a specific mRNA molecule. The
sequence of nucleotides in the mRNA molecule determines the amino acid sequence in a particular protein. mRNA is synthesized from DNA on an as-needed basis, and then rapidly degraded
after a particular protein is synthesized.
Transfer RNA, the smallest type of RNA, interprets the genetic information in mRNA and
brings specific amino acids to the site of protein synthesis in the ribosome. Each amino acid is
recognized by one or more tRNA molecules, which contain 70–90 nucleotides. tRNAs have two
important sites. The 3' end, called the acceptor stem, always contains the nucleotides ACC and
has a free OH group that binds a specific amino acid. Each tRNA also contains a sequence of
three nucleotides called an anticodon, which is complementary to three bases in an mRNA molecule, and identifies what amino acid must be added to a growing polypeptide chain.
tRNA molecules are often drawn in the cloverleaf fashion shown in Figure 22.7a. The acceptor
stem and anticodon region are labeled. Folding creates regions of the tRNA in which nearby
complementary bases hydrogen bond to each other. A model that more accurately depicts the
three-dimensional structure of a tRNA molecule is shown in Figure 22.7b.
Table 22.2 summarizes the characteristics of the three types of RNAs.
▼
FIGURE 22.7 Transfer RNA
a. tRNA–Cloverleaf representation
A
C
C
5'
3'
b. tRNA–Three-dimensional representation
amino acid
acceptor stem
hydrogen bonding between
complementary base pairs
anticodon
Folding of the tRNA molecule creates regions in
which complementary base pairs hydrogen bond
to each other. Each tRNA binds a specific amino
acid to its 3' end and contains an anticodon that
identifies that amino acid for protein synthesis.
TABLE 22.2
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In the three-dimensional model of a
tRNA, the binding site for the amino acid
is shown in yellow and the anticodon is
shown in red.
Three Types of RNA Molecules
Type of RNA
Abbreviation
Function
Ribosomal RNA
rRNA
The site of protein synthesis, found in the ribosomes
Messenger RNA
mRNA
Carries the information from DNA to the ribosomes
Transfer RNA
tRNA
Brings specific amino acids to the ribosomes for
protein synthesis
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TRANSCRIPTION
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22.6 TRANSCRIPTION
The conversion of the information in DNA to the synthesis of proteins begins with transcription—
that is, the synthesis of messenger RNA from DNA.
RNA synthesis begins in the same manner as DNA replication: the double helix of DNA unwinds
(Figure 22.8). Since RNA is single stranded, however, only one strand of DNA is needed for
RNA synthesis.
• The template strand is the strand of DNA used for RNA synthesis.
• The informational strand (the non-template strand) is the strand of DNA not used for
RNA synthesis.
Each mRNA molecule corresponds to a small segment of a DNA molecule. Transcription begins
at a particular sequence of bases on the DNA template using an RNA polymerase enzyme, and
proceeds from the 3' end to the 5' end of the template strand. Complementary base pairing determines what RNA nucleotides are added to the growing RNA chain: C pairs with G, T pairs with
A, and A pairs with U. Thus, the RNA chain grows from the 5' to 3' direction. Transcription is
completed when a particular sequence of bases on the DNA template is reached. The new mRNA
molecule is released and the double helix of the DNA molecule re-forms.
▼
FIGURE 22.8 Transcription
partially unwound
DNA double helix
gene that codes for
a specific protein
non-template
strand of DNA
RNA polymerase
5'
3' end
+
3'
RNA nucleotides
5'
newly made RNA
template
strand of DNA
re-formed
DNA helix
RNA
direction of transcription
In transcription, the DNA helix unwinds and RNA polymerase catalyzes the formation of
mRNA along the DNA template strand. Transcription proceeds from the 3' end to the 5' end
of the template, forming an mRNA molecule with base pairs complementary to the DNA
template strand.
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