NUCLEIC AID Nitrogen-Containing Heterocyclic Bases Five nitrogen-containing (A, C, G, or T)

heterocyclic bases are nucleotide components.

Amost remarkable property of living cells is their ability to Nucleic acids are polymers in which the repeating units, the
produce exact replicas of themselves. Furthermore, cells contain Three of them are derivatives of pyrimidine (Section 17.9), a monomers, are nucleotides.The nucleotide units within a nucleic
all the instructions needed for making the complete organism of monocyclic base with a six-membered ring, and two are acid molecule are linked to each other through sugar–phosphate
which they are a part. The molecules within a cell that are derivatives of purine (Section 17.9), a bicyclic base with fused fi bonds. The resulting molecular structure involves a chain of
responsible for these amazing capabilities are nucleic acids. ve- and sixmembered rings. alternating sugar and phosphate groups with a base group
protruding from the chain at regular intervals. We can now defi
TYPES OF NUCLEIC ACIDS Both of these heterocyclic compounds are bases because they ne, in terms of structure, the two major types of nucleic acids:
contain amine functional groups (secondary or tertiary), and ribonucleic acids and deoxyribonucleic acids
Two types of nucleic acids are found within cells of higher amine functional groups exhibit basic behavior (proton
organisms: acceptors; A ribonucleic acid (RNA) is a nucleotide polymer in which each
1. deoxyribonucleic acid (DNA) of the monomers contains ribose, a phosphate group, and one of
The three pyrimidine derivatives found in nucleotides are the heterocyclic bases adenine, cytosine, guanine, or uracil. Two
2. ribonucleic acid (RNA). thymine (T), cytosine (C), and uracil (U).
Nearly all the DNA is found within the cell nucleus. Its primary changes to this definition generate the deoxyribonucleic acid
function is the storage and transfer of genetic information. This The two purine derivatives found in nucleotides are adenine (A) defi nition; deoxyribose replaces ribose and thymine replaces
information is used (indirectly) to control many functions of a and guanine (G) uracil. A deoxyribonucleic acid (DNA) is a nucleotide polymer in
living cell. In addition, DNA is passed from existing cells to new which each of the monomers contains deoxyribose, a phosphate
cells during cell division. RNA occurs in all parts of a cell. It Adenine is the 6-amino derivative of purine, and guanine is the group, and one of the heterocyclic bases adenine, cytosine,
functions primarily in synthesis of proteins, the molecules that 2-amino-6-oxo purine derivative. A space-fi lling model for guanine, or thymine.
carry out essential cellular functions. The structural distinctions adenine is shown in Figure 22.1. Adenine, guanine, and cytosine
are found in both DNA and RNA. Uracil is found only in RNA, and The alternating sugar–phosphate chain in a nucleic acid
between DNA and RNA molecules are conSidered in All nucleic structure is often called the nucleic acid backbone. This
acid molecules are polymers. A nucleic acid is a polymer in which thymine usually occurs only in DNA.
backbone is constant throughout the entire nucleic acid
the monomer units are nucleotides. Thus the starting point for a Nucleotide Formation The formation of a nucleotide from sugar, structure. For DNA molecules, the backbone consists of
discussion of nucleic acids is an understanding of the structures base, and phosphate can be visualized as occurring alternating phosphate and deoxyribose sugar units; for RNA
and chemical properties of nucleotides molecules, the backbone consists of alternating phosphate and
Important characteristics of this combining of three molecules ribose sugar units. contrasts the generalized backbone structure
NUCLEOTIDES: BUILDING BLOCKS OF NUCLEIC ACIDS into one molecule (the nucleotide) are that for a nucleic acid with the specific backbone structures of DNAs
A nucleotide is a three-subunit molecule in which a pentose and RNAs.
1. Condensation, with formation of a water molecule, occurs at
sugar is bonded to both a phosphate group and a nitrogen- two locations: between sugar and base and between sugar and
containing heterocyclic base. With a three-subunit structure, The variable portion of nucleic acid structure is the sequence of
phosphate. bases attached to the sugar units of the backbone. The sequence
nucleotides are more complex monomers than the
monosaccharides of polysaccharides (Section 18.8) and the 2. The base is always attached at the C-1 position of the sugar. of these base side chains distinguishes various
amino acids of proteins (Section 20.2). A block structural For purine bases, attachment is through N-9; for pyrimidine DNAs from each other and various RNAs from each other. Only
diagram for a nucleotide is bases, N-1 is involved. The C-1 carbon atom of the ribose unit is four types of bases are Found in any given nucleic acid structure.
always in a b configuration and the bond connecting the sugar This situation is much simpler than that for proteins, where 20
Pentose Sugars The sugar unit of a nucleotide is either the and base is a b-N-glycosidic linkage
pentose ribose or the pentose 2!-deoxyribose side-chain entities (amino acids) are available. In both RNA and
DNA, adenine, guanine, and cytosine are encountered as side-
3. The phosphate group is attached to the sugar at the C-5#
Structurally, the only difference between these two sugars position through a phosphate– ester linkage chain components; thymine is found mainly in DNA, and uracil is
occurs at carbon 2!. The 9OH group present on this carbon in found only in RNA
ribose becomes a 9H atom in 2-deoxyribose. (The prefi x deoxy- There are four possible RNA nucleotides, differing in the base
means “without oxygen.”) RNA and DNA differ in the identity of present (A, C, G, or U) Primary nucleic acid structure is the sequence in which
the sugar unit in their nucleotides. In RNA the sugar unit is nucleotides are linked together in a nucleic acid. Because the
ribose9hence the R in RNA. In DNA the sugar unit is 2!- four possible DNA nucleotides, differing in the base present sugar–phosphate backbone of a given nucleic acid does not vary,
deoxyribose9hence the D in DNA
the primary structure of the nucleic acid depends only on the The pairing of A with T and that of G with C are said to be concept in understanding DNA replication is the base pairing
sequence of bases present. complementary. A and T are complementary bases, as are G and associated with the DNA double helix
C.
The following list describes some important points about nucleic DNA replication is the process by which the genome's DNA is
acid structure that . Complementary bases are pairs of bases in a nucleic acid copied in cells. Before a cell divides, it must first replicate its
structure that can hydrogen-bond to each other. The fact that entire genome so that each new cell receives a complete set of
1. Each nonterminal phosphate group of the sugar–phosphate complementary base pairing occurs in DNA molecules explains, chromosomes. This process is fundamental to all life and is
backbone is bonded to two sugar molecules through a 3 ,5 - very simply, why the amounts of the bases A and T present are essential for growth, repair, and reproduction. In eukaryotic
phosphodiester linkage. There is a phosphoester bond to the 5 always equal, as are the amounts of G and C cells, DNA replication takes place during the S-phase of the cell
carbon of one sugar unit and a phosphoester bond to the 3# cycle and involves the coordinated activity of a large number of
carbon of the other sugar. Complementary DNA strands are strands of DNA in a double proteins and enzymes
helix with base pairing such that each base is located opposite its
2. A nucleotide chain has directionality. One end of the complementary base. To understand DNA replication, we must regard the two strands
nucleotide chain, the 5 end, normally carries a free phosphate of the DNA double helix as a pair of templates, or patterns.
group attached to the 5 carbon atom. The other end of the Base-Stacking Interactions The bases in a DNA double helix are During replication, the strands separate. Each can then act as a
nucleotide chain, the 3# end, normally has a free hydroxyl group positioned with the planes of their rings parallel (like a stack of template for the synthesis of a new, complementary strand. The
attached to the 3 carbon atom. By convention, the sequence of coins). Stacking interactions involving a given base and the result is two daughter DNA molecules with base sequences
bases of a nucleic acid strand is read from the 5 end to the 3 parallel bases directly above it and below it also contribute to identical to those of the parent double helix. Let us consider
end. the stabilization of the DNA double helix details of this replication.
3. Each nonterminal phosphate group in the backbone of a Use of the Term “DNA Molecule” a misnomer, even though Under the influence of the enzyme DNA helicase, the DNA
nucleic acid carries a 1 charge. The parent phosphoric acid general usage of the term is common in news reports, in double helix unwinds, and the hydrogen bonds between
molecule from which the phosphate was derived originally had textbooks, and even in the vocabulary of scientists. It is complementary bases are broken. This unwinding process, as
three 9OH groups Two of these become involved in the 3 ,5 - technically a misnomer for two reasons. shown in Figure 22.9, is somewhat like opening a zipper
phosphodiester linkage. The remaining 9OH group is free to
exhibit acidic Behavior9that is, to produce a H" ion. 1. Cellular solutions have pH values such that the phosphate DNA helicases are enzymes that are involved in the unwinding of
groups present in the DNA backbone structure are negatively double-stranded DNA into single-stranded DNA, which is
THE DNA DOUBLE HELIX Like proteins, nucleic acids have charged. This means DNA is actually a multicharged ionic species essential for many processes, including DNA replication, repair,
secondary, or three-dimensional, structure as well as primary rather than a neutral molecule. recombination, and transcription. These enzymes are conserved
structure. The secondary structures of DNAs and RNAs differ, in all organisms and are important for maintaining genomic
and we will discuss them separately. The amounts of the bases 2. The two strands of DNA in a double-helix structure are not
held together by covalent bonds but rather by hydrogen bonds, stability.
A, T, G, and C present in DNA molecules were the key to
determination of the general three-dimensional structure of which are noncovalent interactions. Thus, double-helix DNA is an The bases of the separated strands are no longer connected by
DNA molecules. Base composition data for DNA molecules from entity that involves two intertwined ionic species rather than a hydrogen bonds. They can pair with free individual nucleotides
many different organisms revealed a definite pattern base single molecule present in the cell’s nucleus. As shown in Figure 22.9, the base
occurrence. The amounts of A and T were always equal, and the REPLICATION OF DNA MOLECULES pairing always involves C pairing with G and A pairing with T. The
amounts of C and G were always equal, as were the amounts of pairing process occurs one nucleotide at a time
total purines and total pyrimidines DNA molecules are the carriers of genetic information within a
cell; that is, they are the molecules of heredity. After a free nucleotide has formed hydrogen bonds with a base
Base Pairing A physical restriction, the size of the interior of the of the old strand (the template), the enzyme DNA polymerase
DNA double helix, limits the base pairs that can hydrogen-bond Each time a cell divides, an exact copy of the DNA of the parent verifies that the base pairing is correct and then catalyzes the
to one another. Only pairs involving one small base (a cell is needed for the new daughter cell. The process by which formation of a new phosphodiester linkage between the
new DNA molecules are generated is DNA replication. nucleotide and the growing strand (represented by the darker
Thymine–Adenine Base Pairing (two hydrogen bonds form blue ribbons in Figure 22.9). The DNA polymerase then slides
DNA replication is the biochemical process by which DNA down the strand to the next unpaired base of the template, and
Guanine Base Pairing (three hydrogen bonds form) molecules produce exact duplicates of themselves. The key the same process is repeated.
 inherited from the father, and the other is a copy of one 4) ribosomal RNA (rRNA)
of the chromosomes inherited from the mother 5) transfer RNA (tRNA)
DNA polymerase is the enzyme responsible for catalyzing the  Homologous chromosomes have similar, but not Heterogeneous nuclear RNA (hnRNA)is RNA formed directly by
polymerization of deoxyribonucleotides into a DNA strand. Each identical, DNA base sequences; both code for the same DNA transcription. Post-transcription processing converts the
of the two daughter molecules of double-stranded DNA formed traits but for different forms of the trait (for example, heterogeneous nuclear RNA to messenger RNA.
in the DNA replication process contains one strand from the blue eyes versus brown eyes)
original parent molecule and one newly formed strand. OVERVIEW OF PROTEIN SYNTHESIS We saw in the previous Messenger RNA (mRNA) is RNA that carries instructions for
section how the replication of DNA makes it possible for a protein synthesis (genetic information) to the sites for protein
Though simple in principle, the DNA replication process has synthesis. The molecular mass of messenger RNA varies with the
many intricacies. new cell to contain the same genetic information as its
parent cell. We will now consider how the genetic length of the protein whose synthesis it will direct.
1. The enzyme DNA polymerase can operate on a forming DNA information contained in a cell is expressed in cell operation. Small nuclear RNA (snRNA) is RNA that facilitates the conversion
daughter strand only in the 5#-to-3# direction. Because the two This brings us to the topic of protein synthesis. The synthesis of heterogeneous nuclear RNA to messenger RNA. It contains
strands of parent DNA run in opposite directionsonly one strand of proteins (skin, hair, enzymes, hormones, and so on) is from 100 to 200 nucleotides
can grow continuously in the 5 -to-3 direction. The other strand under the direction of DNA molecules. It is this role of DNA
must be formed in short segments, called Okazaki fragments as that establishes the similarities between parent and Ribosomal RNA (rRNA) is RNA that combines with specific
the DNA unwinds. offspring that we regard as hereditary characteristics. We proteins to form ribosomes, the physical sites for protein
can divide the overall process of protein synthesis into two synthesis. Ribosomes have molecular masses on the order of 3
The breaks or gaps in this daughter strand are called nicks. To phases. The fi rst phase is called transcription and the second million amu. The rRNA present in ribosomes has no
complete the formation of this strand, the Okazaki fragments are translation. The following diagram summarizes the informational function.
connected by action of the enzyme DNA ligase relationship between transcription and translation.
Transfer RNA (tRNA) is RNA that delivers amino acids to the
2. The process of DNA unwinding does not have to begin RIBONUCLEIC ACIDS sites for protein synthesis. Transfer RNAs are the smallest of the
at an end of the DNA molecule. It may occur at any RNAs, possessing only 75–90 nucleotide units. At a nondetail
location within the molecule. the result of this Four major differences exist between RNA molecules and level, a cell consists of a nucleus and an extranuclear region
multiple-site replication process is formation of DNA molecules called the cytoplasm.
“bubbles” of newly synthesized DNA. The bubbles
grow larger and eventually coalesce, giving rise to two . 1. The sugar unit in the backbone of RNA is ribose; it is  TRANSCRIPTION: RNA SYNTHESIS
complete daughter DNAs. Multiple-site replication deoxyribose in DNA. Transcription is the process by which DNA directs the synthesis
enables large DNA molecules to be replicated rapidly. 2. The base thymine found in DNA is replaced by uracil in of hnRNA/mRNA molecules that carry the coded information
RNA (Figure 22.2). In RNA, uracil, instead of thymine, pairs needed for protein synthesis. Messenger RNA production via
Chromosome with (forms hydrogen bonds with) adenine. transcription is actually a “two-step” process in which an hnRNA
molecule is initially produced and then is “edited” to yield the
3. RNA is a single-stranded molecule; DNA is double- desired mRNA molecule
 These histone–DNA complexes stranded (double helix). Thus RNA, unlike DNA, does not
 is an individual DNA molecule bound to a group of contain equal amounts of specifi c bases. Gene is a segment of a DNA strand that contains the base
proteins. Typically, a chromosome is about 15% by mass sequence for the production of a specifi c hnRNA/mRNA
DNA and 85% by mass protein. 4. RNA molecules are much smaller than DNA molecules, molecule.
 Cells from different kinds of organisms have different ranging from 75 nucleotides to a few thousand nucleotides.
numbers of chromosomes. A normal human has 46 A genome is all of the genetic material (the total DNA) contained
Types of RNA Molecules in the chromosomes of an organism
chromosomes per cell, a mosquito 6, a frog 26, a dog
78, and a turkey 82. Chromosomes occur in matched RNA molecules found in human cells are categorized into fi Steps in the Transcription Process The mechanics of
(homologous) pairs. The 46 chromosomes of a human ve major types, distinguished by their function. transcription are in many ways similar to those of DNA
cell constitute 23 homologous pairs. One member of replication. Four steps are involved.
each homologous pair is inherited from the father, and 1) heterogeneous nuclear RNA (hnRNA)
the other is 2) messenger RNA (mRNA) 1. A portion of the DNA double helix unwinds, exposing some
inherited from the mother 3) small nuclear RNA (snRNA) bases (a gene). The unwinding process is governed by the
enzyme RNA polymerase rather than by DNA helicase  THE GENETIC CODE 1. They contain four rRNA molecules and about 80 proteins that
(replication enzyme). Each mRNA molecule has a nucleotide (base) sequence that are packed into two rRNA-protein subunits, one small subunit
determines the amino acid sequence of the protein it directs. To and one large subunit
2. Free ribonucleotides, one nucleotide at a time, align along one allow enough information for the sequencing of the 20 standard
of the exposed strands of DNA bases, the template strand, amino acids found in proteins, sequences of three nucleotides in 2. Each subunit contains approximately 65% rRNA and 35%
forming new base pairs. In this process, U rather than T aligns mRNA molecules (codons) are used to represent each amino protein by mass.
with A in the base-pairing process. Because ribonucleotides acid. Sixty-one of the 64 possible codons represent specific
rather than deoxyribonucleotides are involved in the base 3. A ribosome’s active site, the location where proteins are
amino acids, while the other three are termination codons (stop synthesized by one-at-a time addition of amino acids to a
pairing, ribose, rather than deoxyribose, becomes incorporated signals). The genetic code describes the assignment of mRNA
into the new nucleic acid backbone. growing peptide chain, is located in the large ribosomal subunit.
codons to specific amino acids or stop signals
3. RNA polymerase is involved in the linkage of ribonucleotides, 4. The active site is mostly rRNA, with only one of the
A codon is a three-nucleotide sequence in an mRNA molecule ribosome’s many protein components being present.
one by one, to the growing hnRNA molecule. that codes for a specific amino acid
4. Transcription ends when the RNA polymerase enzyme 5. Because rRNA is so predominant at the active site, the
The genetic code is the assignment of the 64 mRNA codons to ribosome is thought to be a RNA enzyme), that is, a ribozyme.
encounters a sequence of bases that is “read” as a stop signal. specific amino acids (or stop signals).
The newly formed hnRNA molecule and the RNA polymerase 6. The mRNA involved in the
enzyme are released, and the DNA then rewinds to re-form the 1.The genetic code is highly degenerate; that is, many amino
original double helix acids are designated by more than one codon During the five general steps of the translation process, the
following events occur:
Post-Transcription Processing: Formation of mRNA 2. The genetic code is highly degenerate; that is, many amino
acids are designated by more than one codon 1. Activation of tRNA: Each amino acid is attached to a specific
 The RNA produced from a gene through transcription is transfer RNA (tRNA) molecule in a two-step reaction, using ATP
hnRNA, the precursor for mRNA. The conversion of hnRNA 3. The genetic code is almost universal. as an energy source.
to mRNA involves post-transcription processing of the
hnRNA. In this processing, certain portions of the hnRNA 4. An initiation codon exists 2. Initiation: The process begins when an mRNA molecule binds
are deleted and the retained parts are then spliced The genetic code is highly degenerate, and many amino acids are to the small subunit of a ribosome. The first tRNA along with its
together. This process leads us to the concepts of exons and designated by more than one codon. Three amino acids (Arg, amino acid enters the P site on the ribosome and scans the
introns Leu, and Ser) are represented by six codons. Two or more mRNA. The start codon AUG (or rarely GUG) signals the
 An exon is a gene segment that conveys (codes for) genetic codons exist for all other amino acids except Met and Trp, which beginning of the coding region and attracts the initiator tRNA
information. Exons are DNA segments that help express a have only a single codon. The genetic code is almost universal. molecule carrying methionine (or formylmethionine in some
genetic message. The same codon specifies the same amino acid whether the cell organisms) to the P-site of the ribosome.
 An intron is a gene segment that does not convey (code for) is a bacterial cell, a corn plant cell, or a human cell. There is one
genetic information. Introns are DNA segments that 3. Elongation: The ribosome moves along the mRNA, decoding
initiation codon that initiates protein synthesis when it occurs as each codon and linking the appropriate amino acid to the
interrupt a genetic message. the first codon in an amino acid sequence and codes for the preceding one as it proceeds. After a tRNA delivers its amino acid
 A gene consists of alternating exon and intron segments amino acid methionine. UAG, UAA, and UGA are stop cod to the ribosome, it leaves the ribosome from the E site.
 The process of transcription of a gene produces
heterogenous nuclear RNA (hnRNA) that contains both Translation is the process by which mRNA codons are  Translocation is the part of translation in which a ribosome
exons and introns. deciphered and a particular protein molecule is synthesized. The moves down an mRNA molecule three base positions (one
 The hnRNA is then spliced to remove the introns and join substances needed for the translation phase of protein synthesis codon) so that a new codon can occupy the ribosomal A site
together the remaining exons, resulting in messenger RNA are mRNA molecules, tRNA molecules, amino acids, ribosomes,
(mRNA) that carries the genetic information for protein and a number of different enzymes. A ribosome is an rRNA– 4. Termination: The elongation process continues until a stop
assembly. Investigating the function of introns is an active protein complex that serves as the site for the translation phase codon (UAA, UAG, or UGA) is encountered, at which point the
area of biochemical research. of protein synthesis ribosome releases the polypeptide and disassembles.
 Splicing is the process of intron removal, which involves
ribosome such structures: 5. Post-translational processing: After the polypeptide is
snRNA.
synthesized, it may undergo a variety of modifications, such as
folding into its native conformation, phosphorylation or NUCLEIC ACIDS AND VIRUSES Step 5: Separation of the reaction mixture into four parts.
glycosylation
virus is a small particle that contains DNA or RNA (but not both) Step 6: Polynucleotide synthesis with interruption.
 Removal of the initiator methionine residue by a specialized surrounded by a coat of protein and that cannot reproduce
enzyme through a hydrolysis reaction. A second hydrolysis without the aid of a host cell. Viruses do not possess the Step 7: Identifi cation of the reaction mixture components.
reaction then releases the polypeptide chain from its tRNA nucleotides, enzymes, amino acids, and other molecules
carrier. necessary to replicate their nucleic acid or to synthesize proteins
 Covalent modification of a protein, such as the formation of
disulfide bridges between cysteine residues. Vaccine is a preparation containing an inactive or weakened
 Completion of the folding of polypeptides into their active form of a virus or bacterium.
conformations which starts as the polypeptide chain is RECOMBINANT DNA AND GENETIC ENGINEERING
elongated on the ribosome. For proteins with a quaternary
structure, the various components are assembled together. DNA molecules function under various chemical conditions has
opened the door to the fi eld of technology called genetic
Efficiency of mRNA Utilization engineering or biotechnology. Techniques now exist whereby a
Many ribosomes can move simultaneously along a single mRNA “foreign” gene can be added to an organism, and the organism
molecule (Figure 22.25). In this highly efficient arrangement, will produce the protein associated with the added gene.
many identical protein chains can be synthesized almost at the Genetic engineering procedures involve a type of DNA called
same time from a single strand of mRNA. This multiple use of recombinant DNA. Recombinant DNA (rDNA) is DNA that
mRNA molecules reduces the amount of resources and energy contains genetic material from two different organisms.
that the cell expends to synthesize needed protein. Such
complexes of several ribosomes and mRNA are called A restriction enzyme is an enzyme that recognizes specifi c base
polyribosomes or polysomes. sequences in DNA and cleaves the DNA in a predictable manner
at these sequences
A polyribosome is a complex of mRNA and several ribosomes
Transformation is the process of incorporating recombinant
DNA into a host cell. The transformed cells then reproduce,
 MUTATION resulting in large numbers of identical cells called clones.

A mutation is a change in the base sequence of DNA that can Clones are cells with identical DNA that have descended from a
occur during DNA replication. Mutations can lead to changes in single cell
the amino acid sequence during protein synthesis, which can THE POLYMERASE CHAIN REACTION is a method for rapidly
have profound effects on an organism. Mutagens, such as producing multiple copies of a DNA nucleotide sequence.
radiation and chemical agents, can cause mutations. The body
has repair enzymes that recognize and replace altered bases, DNA sequencing is a method by which the base sequence in a
and normally the vast majority of altered DNA bases are repaired DNA molecule (or a portion of it) is determined.
and mutations are avoided. However, occasionally the damage is
not repaired and the mutation persists. Radiation, including The basic steps involved in the DNA sequencing process are as
ultraviolet light from the sun, can be mutagenic and can lead to follows:
serious problems such as skin cancer. Chemical agents, including Step 1: Cleavage using restriction enzymes
nitrous acid, can cause deamination of heterocyclic nitrogen
bases. The use of nitrates and nitrites as preservatives in foods Step 2: Separation into individual components.
such as bologna and hot dogs is a cause of concern because of
their conversion to nitrous acid in the body and possible damage Step 3: Separation into single strands
to DNA.
Step 4: Addition of primer to the single strands.