Nucleic acid chemistry and structure

DNA and RNA are nucleic acids, long, thread-like polymers

made up of a linear array of monomers called nucleotides

All nucleotides contain three components:

1. A nitrogen base

2. A pentose sugar

3. A phosphate residue

Structure of Nucleotide BasesBases are classified as Pyrimidines or Purines

Nucleotide and nucleic acid nomenclature

Phosphodiester linkages in the covalent backbone of DNA

and RNA

The discovery of DNA double

helix

Chargaff's Rule

(A=T, G=C in DNA)

Franklin, Wilkins:

X-ray Diffraction

Refined Structure

Properties of a DNA double helix

The strands of DNA are antiparallel

The strands are complimentary

There are Hydrogen bond forces

There are base stacking interactions

There are 10 base pairs per turn

DNA is a Double-Helix

Primary structure

The base sequence (or the nucleotide sequence)

in polydeoxynucleotide chain

Secondary structure

The secondary structure is defined as the relative

spatial position of all the atoms of nucleotide

residues.

Secondary structure

— DNA double helix structure

•Watson and Crick , 1953

•The genetic material of

all organisms except for

some viruses.

•The foundation of the

molecular biology.James D. Watson

Francis H.C. Crick

The complex folding of large chromosomes within

eukaryotic chromatin and bacterial nucleoids is generally

considered tertiary structure.

Supercoils: double-stranded circular DNA form supercoils if the strands are underwound (negatively supercoiled) or overwound (positively supercoiled).

Tertiary structure

Relaxed supercoiled

• If the strands are overwound,form positively supercoiled;

• If the strands are underwound, form negatively supercoiled.

The DNA in a prokaryotic cell is a

supercoil.

• Supercoiling makes the DNA molecule more compact thus important for its packaging in cells.

Comparison of A, B, and Z forms of DNA

Comparison of A, B, and Z forms of DNA

The Avery-Macleod-McCarty experiment

Palindromes and mirror repeats

DNA structures containing three of four

DNA strands- Hoogsteen pairing

Hoogsteen pairing

DNA structures containing three of four

DNA strands- Guanosine tetraplex

DNA structures containing three of four

DNA strands- H-DNA

Prokaryotic mRNA

Typical right-handed stacking pattern of single-

stranded RNA

Secondary structure of RNAs

Reversible denaturation and annealing

(renaturation) of DNA

Heat denaturation of DNA

DNA hybridization

Some well-characterized nonenzymatic reactions of nucleotides

Some well-characterized nonenzymatic reactions of

nucleotides

Formation of pyrimidine dimers induced by UV light

Chemical agents that cause DNA damage

Chemical agents that cause DNA damage

Alkylating agents- dimethylsulfate

Nucleoside phosphates

The phosphate ester and phosphoanhydride bonds

of ATP

Some coenzymes containing adenosine

Some coenzymes containing adenosine

Some coenzymes containing adenosine

Three regulatory nucleotides

Eukaryotic DNA

• DNA in eukaryotic cells is highly packed.

• DNA appears in a highly ordered form called chromosomes during metaphase, whereas shows a relatively loose form of chromatin in other phases.

• The basic unit of chromatin is nucleosome.

• Nucleosomes are composed of DNA and histone proteins.

Nucleosome

• The chromosomal DNA iscomplexed with five typesof histones.

•H1, H2A, H2B, H3 and H4.

•Histones are very basicproteins, rich in Arginine andLysine.

•Nucleosomes: regular association of DNA with histones to form a structure effectively compacting DNA. ”beads”

Beads on a string

• 146 bp of negatively supercoiled DNA winds 1 ¾ turns around a histone octomer.

• H1 histone binds to the DNA spacer.

Nucleosomes are packaged to form 30 nm fibers

The importance of packing of DNA

into chromosomes

Chromosome is a compact form of the DNA that readily fits inside the cell

To protect DNA from damage

DNA in a chromosome can be transmitted efficiently to both daughter cells during cell division

Chromosome confers an overall organization to each molecule of DNA, which facilitates gene expression as well as recombination.

Functions of DNA

The carrier of genetic information.

The template strand is involved in replication and transcription.

Gene: the minimum functional unit in DNA

Genome: the total genes in a living cell or living beings.

Structures and functions of RNA

Conformational variability of RNA is important for the much more diverse roles of RNA in the cell, when compared to DNA.

Types :

• mRNA: messenger RNA, the carrier of genetic information from DNA to translate into protein

• tRNA: transfer RNA , to transport amino acid to ribosomes to synthesize protein

• rRNA: ribosomal RNA, the components of ribosomes

• hnRNA: Heterogeneous nuclear RNA

• snRNA: small nuclear RNA

RNA structure

RNA molecules are largely single-stranded but there are

double-stranded regions.

3.1 Messenger RNA( mRNA)

• Function: the carrier of genetic information from DNA for the synthesis of protein.

• Comprises only about 5% of the RNA in the cell.

• Composition: vary considerably in size (500-6000 bases in E. coli)

Eukaryotic mRNA Structure

Capping: linkage of 7-methylguanosine to the 5’ terminal residue.

Tailing: attachment of an adennylate polymer (poly A, 20~250 nucleotides) at the 3’ terminal