nuclelc Aclds

DNA (deoxyribonucleic acid) found primarily in the

chromosomal form in the cells nucleus, where it
serve as the repository of genetic information
RNA (ribonucleic acid) present in three major types:
Ribosomal
Messenger
Transfer
Small nuclear, Small interfering, Micro
252 Chapter 9 Nucleic Acids: How Structure Conveys Information
Small nuclear RNAs are found only in the nucleus of eukaryotic cells, and
they are distinct from the other RNA types. They are involved in processing of
initial mRNA transcription products to a mature form suitable for export from
the nucleus to the cytoplasm for translation. Micro RNAs and small interfering
RNAs are the most recent discoveries. SiRNAs are the main players in RNA
interference (RNAi), a process that was first discovered in plants and later in
mammals, including humans. RNAi causes the suppression of certain genes
(see Chapter 11). It is also being used extensively by scientists who wish to
eliminate the effect of a gene to help discover its function (see Chapter 13).
Table 9.1 summarizes the types of RNA.
FIGURE 9.20 The fundamental process
of information transfer in cells. (1) Information
encoded in the nucleotide sequence of DNA is
transcribed through synthesis of an RNA molecule
whose sequence is dictated by the DNA sequence.
(2) As the sequence of this RNA is read (as groups
of three consecutive nucleotides) by the protein syn-
thesis machinery, it is translated into the sequence of
amino acids in a protein. This information transfer
system is encapsulated in the dogma DNA 3 RNA 3
protein.

DNA
Replication
DNA
Transcription
Translation
mRNA
Ribosome
mRNA
Protein
tRNAs
Attached
amino acid
Growing
peptide chain
Replication
DNA replication yields two
DNA molecules identical to the
original one, ensuring transmission
of genetic information to daughter
cells with exceptional fidelity.
Transcription
The sequence of bases in DNA is
recorded as a sequence of
complementary bases in a single-
stranded mRNA molecule.
Translation
Three-base codons on the mRNA
corresponding to specific amino acids
direct the sequence of building a
protein. These codons are recognized
by tRNAs (transfer RNAs) carrying the
appropriate amino acids. Ribosomes
are the machinery for protein
synthesis.
1
2

Table 9.1
The Roles of Different Kinds of RNA
RNA Type Size Function
Transfer RNA Small Transports amino acids to site of protein
synthesis
Ribosomal RNA Several kinds Combines with proteins to form ribosomes,
variable in size the site of protein synthesis
Messenger RNA Variable Directs amino acid sequence of proteins
Small nuclear RNA Small Processes initial mRNA to its mature form in
eukaryotes
Small interfering Small Affects gene expression; used by scientists to
RNA knock out a gene being studied
Micro RNA Small Affects gene expression; important in
growth and development
90410_09_c09_p235-260.indd 252 10/18/07 3:51:28 PM
Nucleic Acid for storage,
transfer and expression of
genetic information



DNA RNA proteins

Cell structure and function
!"#"$% '( )*+,-*,+"% ./ 0,-$".- 1-.2%
1
o
- order of bases in the polynucleotide sequence

2
o
- three-dimensional conformation of the
backbone

3
o
- supercoiling of the molecule
nucleoudes
Three chemical parts:
Nitrogenous bases - aromatic, heterocyclic compound
containing C, H, N and in some cases, O
Aldopentose (sugar) five-carbon carbohydrate
Phosphate groups
nlLrogenous 8ase
yrlmldlne (y) - weakly baslc
Planar
Hydrophobic
Nearly insoluble in water
at physiological pH
Can be stacked atop
each other (or w/
purines)

urlnes (u) - weakly baslc
Very nearly planar
Hydrophobic
Nearly insoluble in
water at physiological
pH
Can be stacked atop
each other (or w/
pyrimidines)

urlnes (unA and 8nA)
yrlmldlnes
CLher blologlcal purlnes
Hypoxanthine and xanthine: rare
constituents of nucleic acids
Uric acid: never found in nucleic acids;
degradation product of N metabolism
N
N
N
N
H
O
H
N
N
N
N
H
O
H
O
H
N
N
N
N
H
O
H
O
H
O
H
hypoxanthine xanthine Uric acid
Modled bases
N
N
NH
N
NH
CH
3
N
N
O
CH
3
NH
2
N
6
-Methyladenine
5-Methylcytosine
HN
N
NH
N
O
NH H
3
C
N
2
-Methylguanine
N
N O
CH
2
OH
NH
2
5-Hydroxymethylcytosine
HN
N
NH
N
O
Hypoxanthine
HN
N
NH
N
+
O
NH H
3
C
CH
3
7-Methylguanine
N
HN
S
O
4-Thiouracil
bases found in
very low
quantities in DNA
and RNA
N
N
NH
N
NH
CH
3
N
N
O
CH
3
NH
2
N
6
-Methyladenine
5-Methylcytosine
HN
N
NH
N
O
NH H
3
C
N
2
-Methylguanine
N
N O
CH
2
OH
NH
2
5-Hydroxymethylcytosine
HN
N
NH
N
O
Hypoxanthine
HN
N
NH
N
+
O
NH H
3
C
CH
3
7-Methylguanine
N
HN
S
O
4-Thiouracil
rlmary SLrucLure
! Nucleotide- the monomer unit of a nucleic acid
= nitrogenous bases + sugar (pentose) + phosphate
group
!"# %"#
8ases: adenlne, guanlne,
cyLoslne& '()*+,-
8ases: adenlne, guanlne,
cyLoslne, ./01+2
Sugar: deoxyrlbose Sugar: deoxyrlbose
phosphaLe phosphaLe
Sugar
nucleoslde
Consists of a base and a sugar
covalently linked together
A base forms a glycosidic linkage
with the sugar
nucleosldes
Conformation can be syn or anti
Sugar and bases lie approximately at right
angles relative to each other
Forms when
a phosphoryl
group
(-PO
3
2-
) is
linked to a
carbohydrat
e hydroxyl
group on the
nucleoside

nucleoude
nomenclaLure
A nucleotide is named from the parent
nucleoside with the suffix
monophosphate added
The position of the phosphate ester is
specified by the number of the carbon atom
at the hydroxyl group to which it is esterified
3,5
phosphodiester bond
Covalent backbone of nucleic acids consist of
alternating deoxyribose or ribose and phosphate
groups
The heterocyclic bases linked to the covalent
backbone via N-glycosidic bonds protrude from the
structural backbone like side chains in proteins
nuclelc Acld
nuclelc Acld
Oligonucleotide short sequence of a nucleic acid
pTpApCpG or TACG
d(TACG)
Chemlcal roperues
Have acidic and basic regions
Phosphate groups of the backbone have negative charges because of
proton dissociation at physiological pH
The ionic character of the negatively charged phosphate backbone
and the polar sugar components establish a hydrophilic region
The variable region of the nitrogenous bases is
hydrophobic
The weakly basic nitrogen atoms and amino groups are not
protonated and carry no charge
Secondary SLrucLure of unA
The secondary structure of DNA was proposed
by James Watson and Francis Crick in 1953
X-ray crystallography data for DNA (Rosalind Franklin, Maurice
Wilkins) showed a regular, repeating structural unit, define atomic
spacing and dimensions of the molecule
Secondary SLrucLure of unA
! Chemical analysis of the A, T, G, C content
(Levine) and calculation of the relative ratios of
A:T and G:C (Chagraffs rule) the amount of A
is always the same as the amount of T and the
amount of G is always the same as the amount of
C
! Bases are possible to form at least two hydrogen
bonds
Consists of two complementary polynucleotide
chains twisted to form a circular staircase-type
structure

Two right-handed, helical, chains are coiled
around a common axis
The two strands run in opposite directions
(antiparallel)
In aqueous environment, the polar, charged,
covalent backbone is on the outside of the helix,
the hydrophobic bases avoid water by turning
toward the inside of the structure
Stabilized by two types of forces
Hydrogen bonds between pairs of complementary bases on opposite
strands
H-bonds between bases on opposite chains determine the alignment of
the helix with the paired bases lying in planes perpendicular to the helix
axis
T: 4 & 3
A: 6 & 1
C: 4, 3, & 2
G: 6, 1 & 2
Stabilized by two types of forces

o Van der Waals or hydrophobic interactions
betweenstacked bases
o The planes of the nucleotide bases are nearly
perpendicular to the common axis and take on a
stacking arrangement like stairs in a circular
staircase
ComplemenLary 8ase alrlng
A-T pairing and C-G pairing
1wo lmporLanL leaLures of nuclelc Aclds
A polynucleotide chain has a sense or
directionality
A polynucleotide chain has individuality,
determined by the sequence of its bases
! right handed double
helix

! 10 base pairs/turn

! Well- defined major
and minor grooves
! wide and deep
major groove,
narrow and shallow
minor groove
! DNA-DNA hybrid
34!"#
right handed double helix
11 base pairs/turn
short and fat form of ds
DNA
major and minor grooves
nearly equal in depth
DNA-RNA or RNA-RNA
hybrids
#4!"#
Left handed double
helix
12 base pairs per turn
Favored in sequences
with alternating PuPy
Nearly flat major
groove,
narrow and deep
minor groove
54!"#
A, 8, Z
A: right-handed, short and broad, 11
bp per turn
B: right-handed, gentle figure, 10 bp
per turn
Z: left-handed, longest, thinnest, 12 bp
per turn


1eruary SLrucLure of unA: Supercolllng
Supercoiling in Prokaryotic DNA
In prokaryotes, the relaxed form is a closed
circle, a result of covalent joining of the two
ends of a linear double helix circular DNA
Supercoiling the result of extra twisting in
the linear duplex form just before covalent
joining of the two double strands
Tertiary Structure- Supercoiling in DNA
Prokaryotic DNA
Lnzymes lnvolved ln Supercolllng
Topoisomerase enzymes that are involved in
changing the supercoiled state of DNA
Class I topoisomerase cut the phosphodiester backbone of one
strand of DNA, pass the other end through and then reseal the
backbone
Class II topoisomerase cut both strands of DNA, pass some of
the remaining DNA helix between the cut ends, and then reseal
DNA
Gyrase
Tertiary Structure-
Supercoiling in DNA
Eukaryotic DNA

Histones have five main
types H1, H2A, H2B,
H3 and H4

Histone core octamer
composed of
(H2A)2(H2B)2(H3)2(H4)2
H1 is relatively easy to
remove from chromatin