Nucleic acids:
- macromolecules made out of units called
nucleotides,
Deoxyribonucleic acid (DNA) and Ribonucleic
acid (RNA):
- Are large polymers made up of monomers
known as nucleotides. When these monomers
combine, the resulting chain is called a
polynucleotide
- signaling.
- Each nucleotide is made up of three parts:
a) a nitrogen-containing ring structure called a
nitrogenous base,
b) a five-carbon sugar,
c) and at least one phosphate group.
The sugar molecule has a central position in the
nucleotide, with the base attached to one of its
carbons and the phosphate group (or groups)
attached to another.
Major Roles of Nucleotides:
- It serves as precursors for RNA and DNA.
- Are ubiquitous in cellular processes:
 (ATP) is used as a free energy carrier for
reactions, transport, work, and other
activities.
 Nucleotides are components of many
important enzymatic cofactors.
 They serve in activating intermediates in
metabolic reactions for example, by
activating glucose in sugar metabolism.
 They often function as metabolic regulators
or signaling agents; for example, cyclic
adenosine monophosphate (cAMP) serves as
a "second messenger" in hormonal
DNA:
- Is the central repository of genetic information,
storing and transmitting it from generation to
generation.
RNA:
- helps in the expression of this genetic
information,
- functioning as an intermediary between DNA
and the synthesis of proteins
Roles of RNA molecules:
 As a messenger (mRNA) in conveying genetic
instructions.
- Stored genetic information is transcribed from
DNA into RNA as messages (messenger RNA
or mRNA).
- The information from the mRNA is, in turn,
translated to direct the synthesis of polypeptide
chain(proteins)
 It forms part of the protein synthesis machinery
of the cell, the ribosome.
 It helps to organize the structure of the
ribosome.
 It participates directly in the ribosome's catalytic
process of forming polypeptides.
 Transfer RNA (tRNA): convey amino acids to
the ribosome for assembly into polypeptides.
 small RNA molecules: involved in base
modification reactions of ribosomal RNA
(rRNA)
 Small interfering RNAs (siRNA): involved in
suppressing gene expression.
 Some RNA molecules possess catalytic activity
and are important in processing mRNA
(ribozymes)
Genes:
- Are segments of DNA that specify particular
proteins or particular species of RNA that are
used in structural or catalytic roles by the cell.

Bases:
- A single gene may be divided into several:
Exons (coding region): expressed regions
and Introns (non-coding region): intervening
regions
- Many genes encode protein products, meaning
that they specify the sequence of amino acids
used to build a particular protein. However, an
RNA copy (transcript) of the gene must first be
made. This type of RNA is called a messenger
RNA (mRNA), as it serves as a messenger
between DNA and the ribosomes.
Genome:
- Is the complete genetic complement of a cell.
- One whole set of all your genes plus all the
DNA between your genes.
- A simple organism might have a genome of
4000 genes;
- humans are approximately 30,000 distinct genes
Chromosome:
- Is a single DNA molecule carrying a set of
genes.
- Centromeres: are complexes of DNA and
proteins that, during mitosis, help to direct the
segregation of chromosomes into daughter cells.
- Telomeres: are DNA regions at the ends of the
chromosomes that stabilize and protect the
chromosome from degredation.
- Humans have 23 pairs of chromosomes.
Bases, Nucleosides, and Nucleotides
- Four Bases in DNA responsible for encoding
genetic information:
1. thymine
2. cytosine
3. adenine belong to the family of
4. Guanine Purines (6 Carbons with
attached 5 Carbons)
 Some other notable members of purine family
includes:
 Caffeine
 Theobromine- found in chocolates
 6-mercaptopurine – anticancer agent
- In RNA, the thymine base is replaced by uracil,
which lacks the methyl group of thymine. The
bases thymine, uracil and cystosine belong to
the pyrimidine family(6 Carbons).
Purines and pyrimidines:
- are weakly basic because they have –NH2
groups.
- Uracil and other pyrimidine bases are not very
water soluble.
- Purine is water soluble, but the derivatives
adenine and guanine are much less so.
- Addition of a polar sugar moiety and ionic
phosphoryl groups, significantly improves the
aqueous solubility of both purines and
pyrimidines.
James Watson and Francis Crick:
- Discovered the DNA double helix, in which
Adenine pairs with Thymine and guanine pairs
with cystosine.
- However, in an aqueous solution of free single
nucleotides there is very little Watson-Crick
pairing; instead, the bases associate by stacking
and by alternative hydrogen-bonding patterns.
 Two important pentose sugars:
- 2-deoxyribose and Ribose

- Single-letter abbreviations are used for the bases

and the lowercase “d” indicates that the sugar is
deoxyribose.
-
The sugars may be phosphorylated, - The lowercase ‘’p’’ represents the 5’-phosphate
-
and in the polymers of DNA and RNA, the sites group.
of phosphorylation are the 3’ and 5’ positions
on the sugar.
Nucleoside:
- combination of sugar and base
Nucleotides:
- When a nucleoside is phosphorylated, the result
is a nucleotide.
Secondary Structure:
- It carry a negative electrical charge, due to
- Refers to the stable, repeating conformational
ionization of the phosphates.
pattern in a polymer.
Nomenclature for Nucleic acids Bases, Nucleosides,
- DNA and RNA both have highly distinctive
and Nucleotides.
secondary structures, deriving from the
Base Deoxyribonucleoside Deoxyribonucleotide properties of their constituent nucleotides
Base Ribonucleoside Ribonucleotide (5’-
(5’-Monophosphate)
Monophosphate)
Thymine Deoxythymidine Deoxythymidylic acid
Uracil Uridine Uridylic acid (uridylate) DNA Secondary Structures:
(Deoxythymidylate) or
or UMP
Cytosine Cytidine
dTMP
Cytidylic Acid
The DNA “double helix”:
Cytosine Deoxycytidine Deoxycytidylic acid - Is the stable solution confirmation of DNA.
(cytidylate) or CMP
(deoxycytidylate) or
Adenine Adenosine Adenylic Acid (adenylate) - Two polynucleotides chains wound around each
dCTMP
or AMP
Adenine
Guanine
Deoxyadenosine
Guanosine
Deoxyadenylic acid
Guanylic Acid (guanylate) other, with complementary pairing of the bases
(deoxyadenylate) or
or GMP
dAMP
in a scheme proposed by James Watson and
Guanine Deoxyguanosine Deoxyguanylic acid Francis Crick.
(deoxyguanylate) or
dGMP

Primary Structure of DNA and RNA

 Notable features of the double helix include
Primary structure of the polynucleotide:
the following:
- Is the sequence of nucleotide residues, when
covalently linked together in a linear chain in a
polynucleotide
- The covalent linkage between the nucleotide
units is through phosphodiesters, with one
phosphate group bonded to two successive
sugars, using the 3’ - OH group of one sugar and
the 5’ – OH group of another.
  The differences of Z-form helix and the A-form
helix from the B-form helix
B-form helix (Right RNA Double helix
handed twist)
 diameter 2.00nm  diameter of helix is
 10 base pairs per turn thicker at 2.6 nm
 one turn covers a  11 base pairs per turn,
length of about 3.4 with a length of 2.9 nm.
nm base pairs are tilted at
 Major groove: wide to the axis of the helix
& deep at 20 degree).
 Minor groove:  major groove is
narrow & less deep narrower and deeper,
 phosphodiester  minor groove wide and
backbone: smooth shallower,
curve
 Rise per base pair is
 The bases lie to the interior of the helix, where only 0.24nm
their planar faces are hidden from solvent. Z-form helix(Left A-form helix (Right
 The bases are stacked on top of one another, handed twist) handed twist)
such that the plane of each base is nearly  12 base pairs per turn  Major groove deeper.
perpendicular to the long axis of the helix.  one turn covers a  Minor groove becomes
 The sugar-phosphate backbone is largely length of about 4.4 shallower,
exposed to solvent. nm  Rise per base pair is
 Phosphodiester only 0.26nm
 The helix has a right-handed twist. It makes a
backbone: zig-zag  The sugar ring has a
complete turn every 3.4 nm, or about 10.5 course different puckering.
residues. The overall diameter of the helix is  slimmer with a  not important in the
approximately 2.0 nm. diameter of ~ 1.8 nm functioning of the cell
 The strands are antiparallel; one strand runs 3`  Major groove is
5` while the other runs 5`  3’. much shallower, and
 There are two grooves (major and minor) in the the Minor groove is
helix, where the edges of the bases exposed to much deeper and
solvent. narrower.
 Overall, the double helix behaves mechanically  important for
like a semi-flexible rod. regulating gene
 Another highly important feature is the joining expression.
of the two strands by Watson-Crick
complementary base pairing:
 Adenine is paired with thymine; guanine is
paired with cytosine.
 The base pairs are joined by hydrogen Unusual DNA Structures
bonds, with two hydrogen bonds joining Inverted repeated sequences (inverted repeats):
- Occurs throughout genomic DNA.
adenine and thymine, and three hydrogen
- have a two-fold symmetry such that the sequence
bonds joining guanine and cytosine.
along a given strand is self-complementary and
 DNA Can Also Form a Left-Handed Helix
can be paired to form a double hairpin or
(Z-form helix) cruciform structure.
- Under certain unusual solution conditions (high - In duplex DNA, the inverted repeats are
concentrations of certain salts or organic palindromes, DNA sequences that read the same
cosolvents) on both strands when read in the same direction.
A. Palindromic inverted repeated sequence
B. Cruciform structure folded from inverted
repeated sequence

Nucleic acids can also form triple helices or triplexes
- Structures with three strands held together by
stacking of the bases and extra hydrogen bonds to
accommodate the third strand.
- Such structures are limited by pH, however, and
are not stable outside of acidic conditions
Certain unusual DNA sequences have the ability to
fold back on themselves repeatedly to form a
quadruplex structure:
- These sequences are enriched in guanine bases.
- Guanine residues hydrogen-bond to each other to
form the four-base structure, known as a G-
quartet, which contains a monovalent ion
coordinated to the four bases.
- G-quartets and quadruplex structures are
important structural features of telomeres.
RNA secondary structure
RNA
- Is generally found as single chains, whereas
DNA naturally occurs as a duplex of two
separate chains.
- The base uracil replaces thymine in RNA.
- Because of complementary base pairing the
chain can frequently be folded back on itself,
forming right-handed double helical regions in
which the strands are arranged in antiparallel
fashion. As in the B-form helix of DNA,
- the bases are paired in complementary fashion,
- and the planar base pairs are stacked on one
another.
- The phosphodiester backbone remains on the
exterior of the helix while the paired bases are
located to the interior.
- The RNA double helix differs from the B-form
helix of DNA in several ways:
 The diameter of RNA helix is thicker at 2.6 nm
 The base pairs are tilted at an appreciable angle
to the axis of the helix (approximately 20
degree).
 A complete turn of the helix requires 11 base
pairs, and occurs over a helical run of the length
2.9 nm.
 The major groove is narrower and deeper, and
the minor groove wider and shallower, than in
the B-form helix.
 The extra - OH group on ribose, versus
deoxyribose, changes the puckering of the sugar
and the overall hydration of the residues, leading
to these differences from the B-form helix.
 The secondary structures of tRNA molecules
resemble a cloverleaf. Notable features hare include
the following characteristics:
 Several (4 - 5) short helical runs of 4 - 6 base
pairs each
 Several single-stranded regions, some forming
loops at the ends of runs of helix (called stem-
loop structures)
 Several modified bases and sugars, often
involving modification by methylation.
 A short stretch of single-stranded RNA- a
bulge- that is not involved in a stem-loop
structure, in the middle of the molecule.
 An exposed single-stranded region at the 3’ end
of the RNA molecule.
 Messenger RNA(mRNA) can also fold back on itself
to form stem-loop structures, which may play a role
in controlling gene expression.
 Ribosomal RNA molecules (rRNA) fold back on
themselves forming:
 Multiple short runs of helix,
 Stem-loop structures,
 and Bulges.
- are often modified to carry unusual bases.
Tertiary and Quaternary Structure
Tertiary structure of a biopolymer:
- Refers to a characteristic repeating structure in
three, dimensions for a single molecule.
The quaternary level of structure:
- Refers to the characteristic spatial arrangement
of two or more different polymer chains.
Tertiary Structure of tRNA:
- For nucleic acids, the tertiary level of structure
includes the packing of helices, bulges, and
single-stranded coils into a stable and more or
less compact body. For example, the Tertiary
Structure of tRNA:

DNA Supercoiling:
- DNA can fold up on itself to form tertiary
structures by supercoiling.
- Refers to the over- or under-winding of a DNA
strand.
- Because DNA is flexible, however, long
molecules can bend enough so that their ends
may be covalently joined to form a continuous,
circular double-stranded molecule
- DNA in this form is described as relaxed and
the molecule so produced is a covalently closed,
circular DNA (ccc DNA)
- We could twist the DNA before joining it
covalently, the twist could go in either direction,
to overwind or underwind the helix.
1. Negative supercoiling
- Is the left-handed coiling of DNA thus
winding occurs in the counterclockwise
direction.
- It is also known as the "underwinding"
of DNA.
2. Positive supercoiling
- Is the right-handed, coiling of DNA thus
winding occurs in the clockwise direction.
- This process is also known as the
"overwinding" of DNA.
3. Plectonemic supercoiling:
- Resembles a twisted thread
- (derived from Greek words for
- "twisted" and "thread")
4. Solenoidal supercoiling:
- Resembles a tubular coil,
- as found in the wiring of electric
- apparatus such as electromagnets.
Nucleosomes
Histones
- Are basic proteins that bind strongly to DNA.
- They help to organize and compact DNA in the
cell nucleus, forming regular units of
approximately 200 base pairs of DNA wound
around an octameric core of different histone
proteins (a nucleosome).
DNA Denaturation and Renaturation:
DNA double helix:
- Is stable under physiological condition of
temperature, salt concentration and pH.
- Raising the temperature or immersing the helix
in a solution with very low amount of salt or
with acidic alkaline pH, will cause the bases to
unpair and unstack, and the strands to separate.
 Helix-coil transition or "melting" of the DNA
double helix.:
- Is the conversion from a double-stranded helical
conformation to separated, highly flexible
conformations of the single strands.
- The temperature at which this occur is donated
as Tm, called the melting temperature or more
formally the transition midpoint temperature.
 Major thermodynamic factors affecting helix
stability include the following phenomena:
 Coulomb repulsion along backbone, from the
charged phosphate, and the attraction of counter
ions to those phosphates.
 Hydrogen bonds between the base pairs.
 The entropically favorable release of waters
solvating individual nucleotides as the helix
forms.
 The relative entropic favorability of a less
organized, "melted" state for the polynucleotide
strands
 Stacking interaction between neighboring bases
and base pairs.
 It is possible to reduce the unfavorable Coulomb
repulsions along the phosphodiester backbone by
adding more salt to solution which helps stabilize
the helix, Solution pH can also affect helix stability.
 Adding alcohols to the solution tends to destabilize
the helix by reducing the amount of stabilizing
interactions with water ;
- at high enough concentration , alcohols and
similar organic compounds may denature or
even precipitate DNA.
Thus bases sequence--- not just base percentage
composition---- affect stability and melting
temperature.
 It is possible to form a double helix of
complementary base pairs with one strand made
entirely of DNA and the other made entirely of
RNA.
 It is also possible to accommodate non-Watson-
Crick base pairs in either a DNA or RNA double
helix.