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1B Nucleotides—Joining a Nucleoside with a Phosphate

1B Nucleotides—Joining a Nucleoside with a Phosphate

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NUCLEOSIDES AND NUCLEOTIDES



687



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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688



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







689



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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690



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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694



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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696



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



697



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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