Deoxyribonucleic Acid (DNA)

Historical Timeline:

Why DNA? (The Genetic Material Debate):

• For decades (1920s–1940s), proteins were considered genetic material due to their structural diversity
• The paradigm shifted between 1928 and 1952 through Griffith's transformation experiment, Avery-MacLeod-McCarty experiment, and Hershey-Chase experiment​
• Watson and Crick's 1953 model was possible because it was consistent with both Chargaff's rules and Franklin's X-ray data

Components of a Nucleotide

A nucleotide has three components:​

1. Nitrogenous Base - The information-carrying component
2. Pentose Sugar - Deoxyribose in DNA (5-carbon sugar)
3. Phosphate Group - One to three phosphate groups; forms the backbone

Nitrogenous Bases in DNA

Nucleotide vs. Nucleoside

• Nitrogenous Base + Pentose Sugar = NUCLEOSIDE
• Nitrogenous Base + Pentose Sugar + Phosphate = NUCLEOTIDE

Salient Features of the Double Helix:

Watson and Crick proposed the double helix model in 1953. The five salient features are:​

1. Two antiparallel polynucleotide chains - One strand runs 5′→3′, the complementary strand runs 3′→5′
2. Sugar-phosphate backbone on outside - The hydrophilic backbone is on the exterior; nitrogenous bases stack inside​
3. Complementary base pairing via hydrogen bonds - A pairs with T (2 H-bonds); G pairs with C (3 H-bonds)
4. Right-handed helix - The helix coils in a clockwise direction​
5. Uniform dimensions - Helix diameter = 2 nm; pitch = 34 Å per turn; ~10 base pairs per turn; distance between adjacent base pairs = 3.4 Å

Base Pairing Rules (Chargaff's Rules):

Chargaff's rule states that in any double-stranded DNA molecule:

• A = T (linked by 2 hydrogen bonds)
• G = C (linked by 3 hydrogen bonds)
• A + G = T + C (total purines = total pyrimidines)

Double-stranded polynucleotide chain

DNA double helix

Forces Stabilising the Double Helix:

• DNA was established as the primary genetic material and formally modeled as a double helix by Watson and Crick in 1953.
• The structural blueprint relied heavily on Erwin Chargaff’s chemical base equivalence rules and Rosalind Franklin’s X-ray diffraction data.
• The fundamental building block of DNA is a nucleotide, which comprises a five-carbon deoxyribose sugar, a phosphate group, and a nitrogenous base.
• A nucleotide is distinct from a nucleoside, as a nucleoside contains only the nitrogenous base and pentose sugar without the attaching phosphate group.
• The double helix is formed by two antiparallel polynucleotide chains running in opposite directions (5′→3′ and 3′→5′) coiled in a clockwise, right-handed fashion.
• The physical architecture places the hydrophilic sugar-phosphate backbone on the exterior, while the information-carrying nitrogenous bases stack flat on the interior.
• Structural stability is maintained horizontally by complementary base pairing (A=T via two hydrogen bonds; G=C via three hydrogen bonds) and vertically by strong covalent phosphodiester bonds.