28.1 Nucleotides and Nucleic Acids

Nucleotides and Nucleic Acids

Nucleotides are the monomers that make up DNA and RNA. Each one contains a nitrogenous base, a pentose sugar, and a phosphate group. Understanding how these pieces fit together is the foundation for understanding genetic information storage, replication, and expression.

Composition of Nucleotides and Nucleic Acids

Every nucleotide has three components joined together:

• Nitrogenous base: either a purine (adenine or guanine, which have a two-ring structure) or a pyrimidine (cytosine, thymine, or uracil, which have a single-ring structure)
• Pentose sugar: deoxyribose in DNA, ribose in RNA. The key structural difference is that deoxyribose lacks a hydroxyl group at the 2' carbon, while ribose has one. That extra $\text{-OH}$ on ribose makes RNA more reactive and less chemically stable than DNA.
• Phosphate group: attached to the 5' carbon of the sugar

A nucleoside is just the base + sugar without the phosphate group. Add the phosphate, and you have a nucleotide. This distinction shows up on exams more often than you'd expect.

DNA (deoxyribonucleic acid) is a double-stranded molecule. Two antiparallel polynucleotide chains are held together by hydrogen bonds between complementary base pairs (A–T and G–C). The sugar-phosphate backbones run along the outside, while the bases stack inward, forming a right-handed double helix.

RNA (ribonucleic acid) is typically single-stranded but can fold back on itself to form secondary structures like hairpin loops through intramolecular base pairing. RNA uses uracil (U) in place of thymine (T).

Base Pairing in Nucleic Acids

The bases fall into two categories based on their ring structure:

A purine always pairs with a pyrimidine. This keeps the width of the double helix consistent.

• A pairs with T (in DNA) or U (in RNA) through two hydrogen bonds
• G pairs with C through three hydrogen bonds

Because G–C pairs have three hydrogen bonds instead of two, DNA regions rich in G–C content are harder to denature (separate) than A–T rich regions. This is a useful detail for understanding melting temperature.

Formation of DNA and RNA Chains

Nucleotides are linked into long polynucleotide chains through phosphodiester bonds. Here's how the linkage works:

1. The phosphate group on the 5' carbon of one nucleotide reacts with the hydroxyl group on the 3' carbon of the next nucleotide.
2. A covalent bond forms between them, releasing water (a condensation reaction).
3. This repeats to build a growing chain with a sugar-phosphate backbone.

The result is a chain with inherent directionality: one end has a free 5' phosphate group (the 5' end), and the other has a free 3' hydroxyl group (the 3' end). New nucleotides are always added to the 3' end, so synthesis proceeds in the $5' \rightarrow 3'$ direction. By convention, sequences are written 5' to 3' as well.

DNA Structure and the Watson-Crick Model

The Watson-Crick model describes DNA as a right-handed double helix with complementary, antiparallel strands. The hydrophilic sugar-phosphate backbones face outward toward the aqueous environment, while the hydrophobic bases stack on top of each other in the interior. Both hydrogen bonding between base pairs and hydrophobic stacking interactions between adjacent bases stabilize the helix.

The double helix has two grooves that differ in size:

• Major groove: wider and more accessible. Many DNA-binding proteins recognize specific sequences by reading the pattern of hydrogen bond donors and acceptors exposed here.
• Minor groove: narrower and less accessible, but still involved in some protein–DNA and drug–DNA interactions.

The structural difference between these grooves matters because proteins don't need to unwind DNA to "read" sequence information; they can detect it through contacts in the grooves.