Introduction

The Building Blocks of Nucleic Acids

This guide will focus on the "central dogma" of molecular biology. We will review the processes responsible
for replicating the nucleic acid DNA, transcribing DNA into RNA, and translating an RNA sequence into a functional
protein. Knowledge of these topics is critical before a more complex understanding of advanced molecular biology
topics is possible. Just as importantly, knowledge of these topics is fundamental to understanding what inside our
bodies allowed us to grow as humans and why our growth is different from that of other organisms.

Figure %: The Central Dogma of Molecular Biology
DNA is the nucleic acid that is responsible for "programming" many or our traits. As the material that composes our
genes, DNA has become one of the most fundamental molecules in molecular biology. n Molecular Genetics, we will
address some fundamentally important questions. We will learn how DNA, our genetic material, is copied and passed
on from generation to generation. We will also address the issue of how the genetic information encoded into a DNA
sequence is used in organisms to express certain proteins, the major constituents of cells. n addressing these major
questions, we will also see how these processes are not perfect and look at how organisms protect against mutations
that could potentially kill cells.
n this topic section, Structure of Nucleic Acids, we will begin our discussion at a more elementary level, investigating
the structure of the nucleic acids DNA and RNA. As DNA and RNA are the major molecules of molecular biology,
understanding their structure is critical to understanding the mechanisms of gene replication and protein synthesis.
The structural elements of each of these molecules play key roles in their performance of the various processes of
the central dogma.


Terms
Anti-paraIIeI - Refers to the orientations of the two single strands that compose a double-stranded DNA helix.
Strands are oriented such that one strand's 5' end is directly across from the other strand's 3' end.
CompIementary - Term used to refer to the natural pairing of the nitrogen bases within DNA and RNA. n DNA,
cytosine pairs with guanine and adenine with thymine. n RNA, the thymine is replaced with uracil, which pairs with
adenine. Each member of these pairs are said to be a "complements" of the other.
Deoxyribose - A five-membered sugar ring that lacks a hydroxyl group at one position, and is the sugar group for
DNA.
DoubIe-stranded heIix - A common structural motif of DNA. Two linear strands of single-stranded DNA fold into a
helical shape stabilized internally by hydrogen bonds between complementary base pairs.
Ester bond - n DNA, refers to the oxygen-carbon linkage between the triphosphate group and the 5' carbon of the
ribose sugar group in a single DNA or RNA nucleotide.
GIycosidic Bond - n DNA, refers to the nitrogen-carbon linkage between the 9' nitrogen of purine bases or 1'
nitrogen of pyrimidine bases and the 1' carbon of the sugar group.
HeIicaI Twist - The angular rotation needed to get from one nucleotide to another in helical structures.
Hydrogen Bonding - Weak, noncovalent linkages between a donor and an acceptor which, when lined up next to
each other, have favorable electrostatic interactions. Provide small amount of stability to DNA and RNA helices.
Provide specificity of the interactions between polynucleotide strands.
Hydrogen Bond Acceptor - A group with at least one free lone pair of electrons. n DNA and RNA, common
acceptor groups include: carbonyls, hydroxyls, and tertiary amines.
Hydrogen Bond Donor - A group with a free hydrogen group. n DNA and RNA, common donors include
secondary amines and hydroxyl groups.
Major groove - n a helix, refers to the larger of the unequal grooves that are formed as a result of the double-
helical structure of DNA. As a result of the patterns of hydrogen bonding between complementary bases of DNA, the
sugar groups stick out at 120 degree angles from each other instead of 180. The major groove is generated by the
larger angular distance between sugars.
Minor groove - n a helix, refers to the smaller of the unequal grooves that are formed as a result of the double-
helical structure of DNA. As a result of the patterns of hydrogen bonding between complementary bases of DNA, the
sugar groups stick out at 120 degree angles from each other instead of 180. The minor groove is generated by the
smaller angular distance between sugars.
Nitrogen Base - One of three components of a nucleotide, nitrogen bases come in two general types: purines and
pyrimidines. Of the four nitrogen bases, adenine and guanine are purines, while cytosine and thymine are pyrimidines.
Through hydrogen bonding, base pairs link in a complementary nature: adenine with thymine and guanine with
cytosine, forming the double-stranded helix of DNA. n RNA, thymine is replaced by uracil.
NucIeic Acid - A chain of nucleotides joined together by phosphodiester bonds. Both DNA and RNA are nucleic
acids.
NucIeotide - A five-membered sugar group with a purine or pyrimidine nitrogen base group attached to its 1' carbon
via a glycosidic bond and one or more phosphate groups attached to its 5' carbon via an ester bond.
Phosphate Backbone - Refers to the structural organization of the DNA double-helix in which the pyrimidine and
purine basic groups face the interior while the phosphate groups line the exterior of the helix. The phosphate
backbone carries a negative charge.
Phosphate Group - One of three components of a nucleotide, comprised of a central phosphorous surrounded by
four oxygens. The phosphate links to the sugar group, carries a negative charge because of the chemical interaction
between phosphorous and oxygen, and forms the exterior of the phosphate backbone.
Phosphodiester Iinkage - n a polynucleotide, refers to the bond between the 3' hydroxyl of a sugar group in a
nucleotide and a phosphate group attached to the 5' carbon of another sugar group.
Pitch - n a helix, refers to the vertical distance traveled in one full turn (360 degrees of twist).
Primary Structure - n DNA and RNA, refers to the linear sequence of base pairs or amino acids in a
polynucleotide chain.
Purine - One of two categories of nitrogen base ring compounds found in DNA and RNA. A purine is a nine-
membered double ring composed of one five-membered joined to a six membered ring containing four nitrogens. See
pyrimidine.
Pyrimidine - One of two categories of nitrogen base ring compounds found in DNA and RNA. A six-membered ring
containing two nitrogens. See purine.
Ribose - The sugar group of RNA, a five-membered sugar ring containing one oxygen and four carbons with one
additional carbon attached to the 4' carbon in the ring and hydroxyl groups attached to the 1', 2', 3', and 5' carbons.
See deoxyribose.
Right Hand RuIe - A trick used to quickly determine the "handedness" or orientation of a helix. n a right-handed
helix, if one extends his or her right hand and traces with fingers along the backbone of the helix, the hand and thumb
move upwards.
Rise - n a helix, the vertical distance traveled when moving from one base pair to the adjacent base pair.
Secondary Structure - n DNA and RNA, the local folding patterns of a polynucleotide based on complementary
base-pairing. Common motifs include alpha helices and bet-pleated sheets.
Sugar Group - One of three components of a nucleotide, a five-ringed carbon sugar, either ribose or deoxyribose in
form. The sugar group bonds to the nitrogen base and to the phosphate group.
Tertiary Structure - n DNA and RNA, the complex three-dimensional form of a polynucleotide.

NucIeotides and NucIeic Acids
Both DNA and RNA are known as nucleic acids. They have been given this name for the simple reason that they are
made up of structures called nucleotides. Those nucleotides, themselves comprising a number of components, bond
together to form the double-helix first discovered by the scientists James Watson and Francis Crick in 1956. This
discovery won the two scientists the Nobel Prize. For now, when we discuss nucleic acids you should assume we are
discussing DNA rather than RNA, unless otherwise specified.
Nucleotides
A nucleotide consists of three things:
A nitrogenous base, which can be either adenine, guanine, cytosine, or thymine (in the case of RNA,
thymine is repIaced by uraciI)
2 A five-carbon sugar, caIIed deoxyribose because it is Iacking an oxygen group on one of its carbons
3 One or more phosphate groups
The nitrogen bases are pyrimidine in structure and form a bond between their 1' nitrogen and the 1' -OH group of the
deoxyribose. This type of bond is called a glycosidic bond. The phosphate group forms a bond with the deoxyribose
sugar through an ester bond between one of its negatively charged oxygen groups and the 5' -OH of the sugar ().

Figure %: A Nucleotide
Nucleic Acids
Nucleotides join together through phosphodiester linkages between the 5' and 3' carbon atoms to form nucleic acids.
The 3' -OH of the sugar group forms a bond with one of the negatively charged oxygens of the phosphate group
attached to the 5' carbon of another sugar. When many of these nucleotide subunits combine, the result is the large
single-stranded polynucleotide or nucleic acid, DNA

Figure %: The Nucleic Acid DNA
f you look closely, you can see that the two sides of the nucleic acid strand shown above are different, resulting in
polarity. At one end of the large molecule, the carbon group is unbound and at the other end, the -OH is unbound.
These different ends are called the 5'- and 3'-ends, respectively
The Helical Structure of DNA shows a single strand of DNA. However, as stated earlier, DNA exists as a double-helix,
meaning two strands of DNA bind together.

Figure %: Double-helical DNA
As seen above, one strand is oriented in the 5' to 3' direction while the complementary strand runs in the 3' to 5'
direction. Because the two strands are oppositely oriented, they are said to be anti-parallel to each other. The two
strands bond through their nitrogen bases (marked A, C, G, or T for adenine, cytosine, and guanine). Note that
adenine only bonds with thymine, and cytosine only bonds with guanine. The nitrogen bases are held together by
hydrogen bonds: adenine and thymine form two hydrogen bonds; cytosine and guanine form three hydrogen bonds.
An important thing to remember about the structure of the DNA helix is that as a result of anti-parallel pairing, the
nitrogen base groups face the inside of the helix while the sugar and phosphate groups face outward. The sugar and
phosphate groups in the helix therefore make up the phosphate backbone of DNA. The backbone is highly negatively
charged as a result of the phosphate groups.
The Importance of the Hydrogen Bond

Hydrogen bonding is essential to the three-dimensional structure of DNA. These bonds donot, however, contribute
largely to the stability of the double helix. Hydrogen bonds are very weak interactions and the orientation of the bases
must be just right for the interactions to take place. While the large number of hydrogen bonds present in a double
helix of DNA leads to a cumulative effect of stability, it is the interactions gained through the stacking of the base
pairs that leads to most of the helical stability.
Hydrogen bonding is most important for the specificity of the helix. Since the hydrogen bonds rely on strict patterns of
hydrogen bond donors and acceptors, and because these structures must be in just the right spots, hydrogen
bonding allows for only complementary strands to come together: A- T, and C-G. This complementary nature allows
DNA to carry the information that it does.
hargaff's Rule
Chargaff's rule states that the molar ratio of A to T and of G to C is almost always approximately equal in a DNA
molecule. Chargaff's Rule is true as a result of the strict hydrogen bond forming rules in base pairing. For every G in a
double-strand of DNA, there must be an accompanying complementary C, similarly, for each A, there is a
complementary paired T.
DNA is a Right-Handed Helix
Each strand of DNA wraps around the other in a right-handed configuration. n other words, the helix spirals upwards
to the right. One can test the handedness" of a helix using the right hand rule. f you extend your right hand with
thumb pointing up and imagine you are grasping a DNA double helix, as you trace upwards around the helix with your
fingers, your hand is moving up. n a left-handed helix, in order to have your hand move upwards with your thumb
pointing up, you would need to use your left hand. DNA is always found in the right-handed configuration.
The Major and Minor Grooves
As a result of the double helical nature of DNA, the molecule has two asymmetric grooves. One groove is smaller
than the other. This asymmetry is a result of the geometrical configuration of the bonds between the phosphate,
sugar, and base groups that forces the base groups to attach at 120 degree angles instead of 180 degrees. The
larger groove is called the major groove while the smaller one is called the minor groove.
Since the major and minor grooves expose the edges of the bases, the grooves can be used to tell the base
sequence of a specific DNA molecule. The possibility for such recognition is critical, since proteins must be able to
recognize specific DNA sequences on which to bind in order for the proper functions of the body and cell to be carried
out. As you might expect, the major groove is more information rich than the minor groove. This fact makes the minor
groove less ideal for protein binding.
haracteristics of the DNA Double-Helix
DNA will adopt two different forms of helices under different conditions--the B- and A-forms. These two forms differ in
their helical twist, rise, pitch and number of base pairs per turn. The twist of a helix refers to the number of degrees of
angular rotation needed to get from one base unit to another. n the B-form of helix, this is 36 degrees while in the A-
form it is 33 degrees. Rise refers to the height change from one base pair to the next and is 3.4 angstroms in the B-
form and 2.6 angstroms in the A-form. The pitch is the height change to get one full rotation (360 degrees) of the helix.
This value is 34 angstroms in the B-form since there are ten base pairs per turn. n the A-form, this value is 28
angstroms since there are eleven base pairs per full turn.
Of the two forms, the B-form is far more common, existing under most physiological conditions. The A-form is only
adopted by DNA under conditions of low humidity. RNA, however, generally adopts the A-form in situations where the
major and minor grooves are closer to the same size and the base pairs are a bit tilted with respect to the helical axis.


ProbIem : Name the four DNA bases. Which two are purines? pyrimidines?
Solution for Problem 1 >>
The four bases are adenine, cytosine, guanine, and thymine. Purine bases are adenine and guanine. Pyrimidine
bases are cytosine and thymine.
Close


ProbIem : Which position on purine bases binds to the ribose? On pyrimidines?
Solution for Problem 2 >>
Purine bases bind from their 9' nitrogen to the ribose group. Pyrimidine bases bind from their 1' nitrogen.
Close


ProbIem : Why is the DNA sugar group called a "deoxyribose"? What group is the DNA ribose group missing and at
what position?
Solution for Problem 3 >>
The DNA sugar group is called a deoxyribose, instead of a ribose, because it lacks an -OH group at its 2' position.
Close


ProbIem : What force holds complementary base pairs together?
Solution for Problem 4 >>
Hydrogen bonds between hydrogen bond donors and acceptors on each base.
Close


ProbIem :

!roblem 5
dentify the three major groups in the figure.
Solution for Problem 5 >>

$olution