7.1 DNA Structure and Function

Nucleotide Components

DNA is the molecule that stores genetic information in all living cells. Its structure directly determines how genetic data gets stored, copied, and read. To understand how genes work, you first need to understand how DNA is built.

Each DNA strand is a long chain of nucleotides. A nucleotide has three parts: a nitrogenous base, a deoxyribose sugar, and a phosphate group. These components connect in a specific way that gives DNA its shape and function.

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Nitrogenous Bases

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

• Purines (adenine and guanine) have two fused carbon-nitrogen rings, making them larger molecules.
• Pyrimidines (thymine and cytosine) have a single ring, making them smaller.

This size difference matters for base pairing. A purine always pairs with a pyrimidine, which keeps the width of the double helix consistent. The specific pairings are A with T (held by 2 hydrogen bonds) and C with G (held by 3 hydrogen bonds). Because C-G pairs have an extra hydrogen bond, regions of DNA rich in C-G pairs are more stable and harder to separate.

This complementary base pairing is what makes accurate DNA replication and transcription possible: each strand serves as a template for building its partner.

Sugar-Phosphate Backbone

Deoxyribose is a five-carbon (pentose) sugar. It's called "deoxy" because it lacks a hydroxyl group ($-OH$) at the 2' carbon, unlike ribose in RNA. This missing $-OH$ group makes DNA more chemically stable than RNA.

Phosphate groups link nucleotides together by connecting the 5' carbon of one sugar to the 3' carbon of the next through a phosphodiester bond. This creates the repeating sugar-phosphate backbone of each strand.

The two strands run in opposite directions: one goes 5' to 3', the other 3' to 5'. This antiparallel arrangement is critical for replication and transcription enzymes, which can only work in the 5' to 3' direction. The phosphate groups carry a negative charge, giving the entire DNA molecule an overall negative charge.

DNA Structure

Double Helix Configuration

DNA's iconic shape is a double helix: two complementary strands wound around each other. Key features of this configuration:

• The strands are antiparallel, running in opposite directions (one 5'→3', the other 3'→5').
• The sugar-phosphate backbones face outward, forming the structural "rails" of the molecule.
• The nitrogenous bases point inward, pairing with their complements through hydrogen bonds.
• These hydrogen bonds between A-T and C-G pairs hold the two strands together and stabilize the helix.

Think of it like a twisted ladder: the sugar-phosphate backbones are the side rails, and the base pairs are the rungs.

Grooves and Base Accessibility

When the two strands wind around each other, they don't produce a perfectly symmetrical surface. Instead, two types of grooves form along the helix:

• The major groove is wider and deeper. Proteins like transcription factors and other DNA-binding proteins access the bases here to "read" the genetic sequence without unwinding the helix.
• The minor groove is narrower and shallower. Certain proteins, including histones and some DNA repair enzymes, interact with DNA through this groove.

The pattern of hydrogen bond donors and acceptors exposed in each groove differs depending on the base pair sequence. This gives each stretch of DNA a unique surface that specific proteins can recognize and bind to.

Base Stacking and Stability

Beyond hydrogen bonding between base pairs, a second force stabilizes the double helix: base stacking interactions.

• Base pairs sit flat and stack on top of each other, like rungs on a ladder.
• The aromatic rings in adjacent bases interact through van der Waals forces and $\pi$-$\pi$ stacking interactions, where the electron clouds of neighboring rings attract each other.
• These stacking interactions are actually a larger contributor to helix stability than hydrogen bonding alone.
• Stacking also keeps the hydrophobic bases tucked inside the helix, away from the surrounding water, which is thermodynamically favorable.