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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