Nucleic acid structure

& function
 DNA as a genetic material
 Fred Griffith in 1928- on the transfer of virulence in
the pathogen Streptococcus pneumoniae- also first
showed that DNA was the genetic material
 If heated virulent bacteria and injected them into mice-
the mice were not affected (no pneumococci)
 When he injected a combination of killed virulent
bacteria and a living nonvirulent strain-the mice died
(recovered living virulent bacteria from the dead mice)
 Griffith called this change of nonvirulent bacteria into
virulent pathogens- TRANSFORMATION
 Oswald T. Avery and his colleagues- selectively
destroyed constituents in purified extracts of virulent
pneumococci, using enzymes that would hydrolyze
DNA, RNA, or protein
 Also exposed nonvirulent pneumococcal strains to the
treated extracts
 Transformation of the nonvirulent bacteria was blocked
only if the DNA was destroyed- suggesting that DNA
was carrying the information required for transformation
 Therefore, O. T. Avery, C.M. Mac Leod, and M.J.
McCarty in 1944- DNA carried genetic information
 There exist a relationship between DNA, RNA, and
protein
 Replication- DNA is copied
 Transcription- expression of the information encoded
in the base sequence of DNA with the synthesis of an
RNA copy of the DNA sequence making up a gene
 A gene is a DNA segment or sequence that codes for a
polypeptide, an rRNA, or a tRNA
 The sequence corresponding to a gene is located only
on one of the two complementary DNA strands
 Different genes may be encoded on opposite strands.
 The RNA that carries information from DNA and
directs protein synthesis is messenger RNA (mRNA)
 Translation/ protein synthesis- the genetic
information in the form of an mRNA nucleotide
sequence is translated and governs the synthesis of
protein- a. acid sequence of a protein is a direct
reflection of the base sequence in mRNA
 In turn the mRNA nucleotide sequence is a
complementary copy of a portion of the DNA genome
 Introduction
– Each cell of our bodies contains thousands of different proteins

– the transmission of hereditary information takes place in the

nucleus, more specifically in structures called chromosomes

– The hereditary information was thought to reside in genes

within the chromosomes

– Chromosomes are made up largely of proteins called histones

and nucleic acids
 Nucleic acids

Backbones of chromosomes

Ribonucleic acids (RNA)

Nucleic acids

Deoxyribonucleic acids (DNA)

 Nucleic acids

DNA stores the genetic information of an organism and

transmits that information from one generation to another

RNA translates the genetic information contained in DNA into

proteins needed for all cellular function

RNA and DNA are unbranched polymers (monomers: nucleotides)

 Nucleotide

A nucleotide is composed of:

• Nitrogen-containing bases (amines)

• Sugars (monosaccharides)
• Phosphate

Phosphate
 Bases

N H2 O O
4
CH3
3 N 5 N HN HN
2 6
N O N O N O N
1
H H H
Pyri mi dine Cytosine (C) Thymine (T) Uraci l (U)
(DNA and (DNA onl y) (in RNA only)
some RNA)

6 7 N H2 O
1 5 N
N N N HN N
8
2 N9
N 4 N N H 2N N N
3
H H H
Puri ne Adenine (A) Guani ne (G)
(DNA and RNA) (DNA and RNA)
 Sugars (monosaccharide)

RNA contains:
• D-Ribose sugar

DNA contains:
• 2-Deoxy-D-Ribose sugar (without O on carbon 2)
 Nucleoside

When a N atom of the base forms a glycosidic bond to C1’ of a sugar

Base + Sugar Nucleoside

O O
uracil O
CH3
HN
HN
N O N -D -ribos ide 1
H H 5' O N a -N -glycosid ic
HOCH2 O bonß-N-glycosidic
d bond
hymine (T) Uraci l (U) 1'
NA onl y) (in RNA only) 4' H H
H 3' 2' H anomeric
HO OH carb on

O
Urid ine

HN N
 Nucleoside

To name a nucleoside derived from a pyrimidine base, use the suffix “-idine”.

To name a nucleoside derived from a purine base, use the suffix “-osine”.
For deoxyribonucleosides, add the prefix “deoxy-”.
 Nucleotide

A nucleotide forms with the −OH on C5’ of a sugar bonds to

phosphoric acid

NH2 NH2
Phosphate ester bond
N N

O O O O N
N 5’
5’
O- P OH + HO CH2 O- P O CH2
O O
-
O- 1’ O

OH OH

deoxycytidine and phosphate deoxycytidine monophosphate (dCMP)

A nucleotide

The name cytidine 5′-monophosphate is abbreviated as CMP.

 Nucleotide

The name deoxyadenosine 5’-monophosphate is abbreviated as dAMP.

 2. Primary structure of DNA and RNA
Polynucleotide
Carry all information
for protein synthesis.

Phosphodiester
bond

Sequence of nucleotides.

Each phosphate is linked to C3’ and C5’ of two sugars.

 Primary structure of DNA and RNA

A nucleoside = Base + Sugar

A nucleotide = Base + Sugar + Phosphate

A nucleic acid = A chain of nucleotides

Like amino acids (C-terminal and N-terminal):

Base sequence is read from the C5’ (free phosphate) end to the C3’ (free hydroxyl) end.

-ACGU-
 Secondary structure of DNA

• The DNA model is proposed by 5’ 3’

Watson and Crick in 1953.

• Two strands of polynucleotide form a

double helix structure like a spiral.
Sugar phosphate
backbone
3D structure

• Hydrogen bonds link paired bases:

Adenine-Thymine (A–T)
Guanine-Cytosine (G-C)

• Sugar-Phosphate backbone is
hydrophilic and stays on the outside
(bases are hydrophobic).
5’
3’
Complementary base pairs

A-T base pair

2 H bonds

G-C base pair

3 H bonds
 Higher structure of DNA

• DNA is coiled around proteins called histones.

• Histones are rich in the basic amino acids

• Acidic DNA basic histones attract each other and form a

chain of nucleosomes.

Core of eight histones

Higher structure of DNA

Chromatin:
Condensed nucleosomes
 Higher structure of DNA

Chromatin fibers are organized into loops, and the loops into the bands
that provide the superstructure of chromosomes.
 Chromosome & Gene

- DNA molecules contain several million nucleotides, while RNA

molecules have only a few thousand.

- DNA is contained in the chromosomes of the nucleus, each

chromosome having a different type of DNA.

- Humans have 46 chromosomes (23 pairs), each made up of

many genes.

- A gene is the portion of the DNA molecule responsible for the

synthesis of a single protein (1000 to 2000 nucleotides).
 NUCLEIC ACID STRUCTURE

 DNA- 2′-deoxyribonucleosides of adenine, guanine, cytosine,

thymine
 RNA- composed of the ribonucleosides of adenine, guanine,
cytosine, uracil (instead of thymine)
 In both DNA and RNA- nucleosides + phosphate groups to
form long polynucleotide chains
 DNA STRUCTURE

 DNA-composed of two polynucleotide chains coiled together to

form a double helix 2.0 nm in diameter
 Each chain contains purine and pyrimidine
deoxyribonucleosides joined by phosphodiester bridges
 Two adjacent deoxyribose sugars are connected by a phosphoric
acid molecule esterified to a 3′- hydroxyl of one sugar and a 5′-
hydroxyl of the other
 Purine and pyrimidine bases are attached to the 1′-carbon of the
deoxyribose sugars and extend toward the middle of the
cylinder formed by the two chains
 They are stacked on top of each other in the center, one base
pair every 0.34 nm
 Wide major groove
 Narrower minor groove
 Each base pair rotates 36° around the cylinder with respect to
adjacent pairs so that there are 10 base pairs per turn of the
helical spiral
 Each turn of the helix has a vertical length of 3.4 nm
 Helix is right-handed
 Two backbones are antiparallel or run in opposite directions
with respect to the orientation of their sugars
 One end – exposed 5′-hydroxyl group- phosphates attached
 Other end has a free 3′-hydroxyl group
 If the end of a double helix is examined, the 5′ end of one strand
and the 3′ end of the other are visible
 In a given direction one strand is oriented 5′ to 3′ and the other, 3′
to 5′
STRUCTURAL FORM OF
DNA
 RNA molecules

Transmits the genetic information needed to operate the cell.

1. Ribosomal RNA (rRNA)

Most abundant RNA – is found in ribosomes: sites for protein synthesis.

2. Messenger RNA (mRNA)

Carries genetic information from DNA (in nucleus) to ribosomes (in cytoplasm)
for protein synthesis. They are produced in “Transcription” from DNA.

3. Transfer RNA (tRNA)

The smallest RNA. Translates the genetic information in mRNA and brings specific
Amino acids to the ribosome for protein synthesis.
 Organization of DNA in cells
 Prokaryotes- closed circle
 Double helix twisted into supercoiled DNA
 Associated with basic proteins but not with the histones (histone like proteins)
 Coiled chromatin like structure
 Eukaryotes- DNA highly organized in chromatin
 Associated with a variety of proteins- histones
 Five types of histones: H1, H2A, H2B, H3, and H4
 Eight histone molecules (two each of H2A, H2B,H3 and H4) form an ellipsoid about
11 nm long and 6.5 to 7 nm in diameter
 Histone complex + DNA is called a nucleosome
 Chromatin looks like a string of beads
 DNA between the beads or nucleosomes, the linker region, varies in length from 14 to
over 100 base pairs
 H1 associates with linker regions to aid the folding of DNA into more complex
chromatin