Nucleic Acid Structure: DNA and RNA – Composition, Linkage, and Helical Forms

Study Guide - Smart Notes

Tailored notes based on your materials, expanded with key definitions, examples, and context.

Nucleic Acids: Structure and Composition

Introduction to Nucleic Acids

Nucleic acids are essential biopolymers that store and transmit genetic information in all living organisms. The two main types are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Both are polymers of nucleotides, joined by phosphodiester linkages, but differ in chemical stability and function.

DNA is a polymer of A, G, C, and T deoxynucleotides.
RNA is a polymer of A, G, C, and U ribonucleotides.
DNA is more chemically stable than RNA due to the absence of a 2'-OH group on the ribose sugar.

Nucleotides and Nucleosides

Structure of Nucleotides

Nucleotides are the building blocks of nucleic acids, each consisting of a nitrogenous base, a pentose sugar, and one or more phosphate groups.

Nucleoside: Consists of a pentose sugar and a nitrogenous base (no phosphate).
Nucleotide: Nucleoside with one or more phosphate groups attached.
Pentose sugar is either ribose (RNA) or deoxyribose (DNA).
Phosphate group attaches at the 5' carbon of the sugar.

Chemical Structures of Nucleotide Bases

Nitrogenous bases are classified as purines or pyrimidines:

Purines: Adenine (A), Guanine (G) – two heterocyclic rings, 9 atoms total.
Pyrimidines: Cytosine (C), Thymine (T, DNA only), Uracil (U, RNA only) – single heterocyclic ring, 6 atoms total.
Attachment to sugar: N-9 atom (purines) or N-1 atom (pyrimidines) links to the 1' carbon of the sugar.

Chemical Structure of Ribose Sugars

The pentose sugar in nucleic acids is numbered from 1' to 5'. The base attaches at the 1' carbon. The key difference between ribose and deoxyribose is at the 2' position:

Ribose: Has an OH group at 2'.
Deoxyribose: Has an H at 2'.

Linkage of Sugar to Base and Phosphate

The base is linked to the sugar via a β-1'-N-glycosidic bond. The phosphate group is attached to the 5' carbon of the sugar, forming nucleotides such as cytidylate (CMP) and adenosine monophosphate (AMP).

Polymerization and Primary Structure

Phosphodiester Linkage and Directionality

Nucleic acids are polymers of nucleotides connected by phosphodiester bonds, which link the 3' hydroxyl of one sugar to the 5' phosphate of the next. This gives the strand a directionality (5' to 3').

Each strand has a 5' phosphate group and a 3' hydroxyl group.
Sequence is always specified from 5' to 3'.

Phosphate Group Chemistry

Nucleotides are strong acids due to their phosphate groups. The phosphate can exist as monoester or diester forms, with different pKa values:

Phosphomonoesters: and
Phosphodiesters: Only one ionizable group, slightly higher than monoesters, but still < 2.

Chemical Stability: DNA vs. RNA

Stability Differences

RNA is less chemically stable than DNA due to the presence of the 2'-OH group, which can participate in base-catalyzed hydrolysis, breaking the polymer chain. DNA lacks this group, making it more suitable for long-term genetic storage.

RNA can form 2',3'-cyclic monophosphate intermediates during hydrolysis.
DNA's stability is crucial for its role in heredity.

Secondary Structure of Nucleic Acids

Double-Helical Structure and Base Pairing

DNA and some RNA molecules can form double-helical secondary structures. In the B-form helix, the two strands are held together by specific base pairing:

Guanine–Cytosine (G–C): 3 hydrogen bonds
Adenine–Thymine (A–T): 2 hydrogen bonds
Strands are antiparallel (run in opposite directions).
Hydrophobic bases are on the inside; sugar-phosphate backbone is on the outside.

Watson-Crick Model

The Watson-Crick model describes the double-helical structure of DNA, with complementary base pairing and antiparallel orientation.

If one strand is 5' ATCGCGA 3', the complementary strand is 3' TAGCGCT 5'.

Forms of DNA Helix: A, B, and Z

B-DNA Structure

B-DNA is the most common form under physiological conditions. It is a right-handed helix with the following features:

Diameter: ~20 Å
Bases per turn: 10.5
Rise per base pair: 3.4 Å
Major groove: wide and deep; minor groove: narrow and deep
Sugar pucker: C2' endo

A-DNA Structure

A-DNA is favored under dehydrating conditions and in RNA-RNA or RNA-DNA duplexes. It is also right-handed but has a wider diameter and different groove dimensions:

Diameter: ~26 Å
Bases per turn: 11
Rise per base pair: 2.6 Å
Sugar pucker: C3' endo

Z-DNA Structure

Z-DNA is a left-handed helix, favored by alternating purine-pyrimidine sequences and high salt conditions. It has a zig-zag backbone and is less common:

Diameter: ~18 Å
Bases per turn: 12
Rise per base pair: 3.7 Å
Sugar pucker: C2' endo for pyrimidines, C3' endo for purines

Major and Minor Grooves

Relationship to Base Pairs

The major and minor grooves of the DNA helix are determined by the orientation of the base pairs. These grooves are important for protein-DNA interactions and regulation.

Major groove: wider, more accessible for protein binding.
Minor groove: narrower, less accessible.
Hydrogen bonds in base pairs are oriented relative to these grooves.

Summary Table: Comparison of DNA Helical Forms

Feature	B-DNA	A-DNA	Z-DNA
Helix Handedness	Right	Right	Left
Diameter (Å)	~20	~26	~18
Bases per Turn	10.5	11	12
Rise per Base Pair (Å)	3.4	2.6	3.7
Major Groove	Wide, deep	Deep, narrow	Almost none
Minor Groove	Narrow, deep	Very narrow	Narrow, deep
Sugar Pucker	C2' endo	C3' endo	C2' endo (pyrimidines), C3' endo (purines)

Key Equations

Phosphodiester bond formation:
Base pairing: (3 H-bonds), (2 H-bonds)

Example Application

DNA Nanotechnology: The predictable base pairing and structural features of DNA are exploited in nanotechnology to build complex molecular structures.
Genetic Information Storage: DNA's chemical stability makes it ideal for long-term storage of genetic information in cells.

Additional info: The notes also reference the importance of DNA's stability for its biological function, and the role of major/minor grooves in protein-DNA interactions.