Chapter 17

Nucleotides and Nucleic acids

Chemistry 20

Introduction

– Each cell of our bodies contains thousands of different proteins.

– How do cells know which proteins to synthesize out of the extremely large number of possible amino acid sequences?

– the transmission of hereditary information took place in the nucleus, more specifically in structures called chromosomes.

– The hereditary information was thought to reside in genes within the chromosomes.

– Chemical analysis of nuclei showed chromosomes are made up largely of proteins called histones and nucleic acids.

Nucleic acids

Backbones of chromosomes

Ribonucleic acids (RNA)

Deoxyribonucleic acids (DNA)

RNA and DNA are polymers (monomers: nucleotides).

Nucleic acids

A nucleotide is composed of:

• Nitrogen-containing bases (amines)• Sugars (monosaccharides)• Phosphate

Nucleotide

Phosphate

Bases

HN

NO

H

N

N

NH2

H

HN

N

H

CH3

Uracil (U)(in RNA only)

Thymine (T)(DNA only)

Cytosine (C)(DNA andsome RNA)

N

N

Pyrimidine

1

2

3

4

5

6

HN

N N

NO

HH2N

Guanine (G)(DNA and RNA)

N

N N

N

NH2

HAdenine (A)

(DNA and RNA)

N

N N

N

HPurine

1

2

3

4

56 7

8

9

O O

O O

Sugars (monosaccharide)

RNA contains: • Ribose sugar

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

When a primidine or purine forms a glycosidic bond to C1’ of a sugar (ether ribose or deoxyribose).

Nucleoside

Base + Sugar Nucleoside

HH

HH

OHOCH2

HO OH

O

O

HN

N

anomericcarbon

a -N-glycosidicbond

Uridine

-D-riboside

uracil

1'

2'3'

4'

5'1

HN

NO

H

N

N

NH2

H

HN

N

H

CH3

Uracil (U)(in RNA only)

Thymine (T)(DNA only)

Cytosine (C)(DNA andsome RNA)

N

N

Pyrimidine

1

2

3

4

5

6

HN

N N

NO

HH2N

Guanine (G)(DNA and RNA)

N

N N

N

NH2

HAdenine (A)

(DNA and RNA)

N

N N

N

HPurine

1

2

3

4

56 7

8

9

O O

O O

ß-N-glycosidic bond

Nucleotide

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

phosphoric acid.

O-

O-

O

P OH +

deoxycytidine and phosphate

HO CH2

O

NH2

N

N

OH

O

5’ 5’

A nucleotide

1’

Phosphate ester bond

Primary structure of DNA and RNA

Sequence of nucleotides.

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

Carry all information for protein synthesis.

A nucleoside = Base + Sugar

A nucleotide = Base + Sugar + Phosphate

A nucleic acid = A chain of nucleotides

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

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

-ACGU-

Primary structure of DNA and RNA

• Two strands of polynucleotide form a double helix structure like a spiral.

• 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).

Secondary structure of DNA

5’

5’

3’

3’

Sugar phosphate backbone

3D structure

Secondary structure of DNA

Complementary base pairs

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 units

called nucleosomes.

Core of eight histones

Higher structure of DNA

Chromatin:Condensed nucleosomes

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

Higher structure of DNA

Difference between DNA & RNA

1. DNA has four bases: A, G, C, and T. RNA has four bases: A, G, C, and U.

2. In DNA: Sugar is 2-deoxy-D-ribose. In RNA: Sugar is D-ribose.

3. DNA is almost always double-stranded (helical structure). RNA is single strand.

4. RNA is much smaller than DNA.

RNA molecules

Transmits the genetic information needed to operate the cell.

2. Messenger RNA (mRNA)

1. Ribosomal RNA (rRNA)

3. Transfer RNA (tRNA)

Most abundant RNA – Contains ribosomes: sites for protein synthesis.

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

Smallest RNA. Translates the genetic information in mRNA and brings specific Amino acids to the ribosome for protein synthesis.

Genes

A section of a DNA molecule that contains a specific sequence of the four bases (A, G, T, and C)

1000 to 2000 nucleotides

Base sequence of the gene carries the information to produce one protein molecule.

Change of sequence New protein

Functions of DNA

1. It reproduces itself (Replication)

2. It supplied the information to make up RNA, proteins, and enzymes.

(chapter 18)

Replication

Separation of the two original strands and synthesis

of two new daughter strands using the original strands as templates.

By breaking H-bonds

Replication

Replication is bidirectional: takes place at the same speed in both directions.

Replication is semiconservative: each daughter molecule has one parental strand

and one newly synthesized one.

Origin of replication: specific point of DNA where replication begins.

Replication fork: specific point of DNA where replication is proceeding.

Replication

Leading strand: is synthesized continuously in the 3’ 5’ direction toward the replication fork.

Lagging strand: is synthesized discontinuously in the 5’ 3’ direction away from the replication fork.

Replication

Replisomes: assemblies of “enzyme factories”.

Component Function

HelicasePrimaseClamp proteinDNA polymeraseLigase

Unwinds the DNA double helixSynthesizes primersThreads leading strandJoins assembled nucleotidesJoins Okazaki fragments in lagging strand

Unwinds the DNA double helix.

•Replication of DNA starts with unwinding of the double helix.

•Unwinding can occur at either end or in the middle.

•Attach themselves to one DNA strand and cause separation of the double helix.

Helicases

Catalyze the synthesis of primers.

Primers: are short nucleotides (4 to 15).

•They are required to start the synthesis of both daughter strands.

•Primases are placed at about every 50 nucleotides in the lagging strand synthesis.

Primases

Catalyze the formation of nucleotides.

Joins the nucleotides to produce a new strands

DNA Polymerase