Nucleic Acids: Structure, Properties, and Biological Functions

4.1 Nucleic Acids – Informational Macromolecules

Introduction to Nucleic Acids

Nucleic acids are essential informational macromolecules responsible for the storage, transmission, and expression of genetic information in all living organisms. The two main types are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

• DNA stores genetic information.

• RNA is involved in gene expression and regulation.

Chemical Structure of DNA and RNA

• Both DNA and RNA are polymers of nucleotides.

• Each nucleotide consists of a phosphate group, a pentose sugar (deoxyribose in DNA, ribose in RNA), and a nitrogenous base.

• DNA contains the bases adenine (A), guanine (G), cytosine (C), and thymine (T).

• RNA contains adenine (A), guanine (G), cytosine (C), and uracil (U) instead of thymine.

Purine and Pyrimidine Bases

• Purines: Adenine (A) and Guanine (G) – double-ring structures.

• Pyrimidines: Cytosine (C), Thymine (T, in DNA), and Uracil (U, in RNA) – single-ring structures.

Nucleosides and Nucleotides

• Nucleoside: Nitrogenous base + sugar.

• Nucleotide: Nitrogenous base + sugar + phosphate group.

• Examples:

  • Adenosine (nucleoside), Adenosine monophosphate (AMP, nucleotide)

  • Cytidine (nucleoside), Cytidine monophosphate (CMP, nucleotide)

Properties of Nucleotides

• Acidity: Nucleotides are strong acids due to the phosphate group.

• Ionization: Primary ionization occurs at low pH; secondary ionization and base protonation/deprotonation occur at neutral pH.

• Tautomerization: Bases can exist in different tautomeric forms (e.g., amino/imino, keto/enol).

• UV Absorption: Nucleotides absorb UV light at ~260 nm, useful for detection and quantification.

Phosphodiester Linkage

• Nucleotides are joined by phosphodiester bonds between the 3' hydroxyl of one sugar and the 5' phosphate of the next.

• Nucleic acid synthesis uses activated nucleotides (e.g., nucleoside triphosphates).

4.2 Primary Structure of Nucleic Acids

Nature and Significance of Primary Structure

• The primary structure is the linear sequence of nucleotides in a nucleic acid strand.

• Conventionally written from the 5' end to the 3' end (e.g., 5'-ACGTT-3').

• Sequence determines the genetic information carried by the molecule.

4.3 Secondary and Tertiary Structures of Nucleic Acids

Secondary Structure: The DNA Double Helix

• Secondary structure refers to the 3D arrangement of nucleotide residues, such as the double helix.

• Watson and Crick proposed the double helix model, supported by X-ray diffraction data (R. Franklin).

• Base pairing: A pairs with T (or U in RNA), G pairs with C via hydrogen bonds.

• Chargaff's rules: %A = %T and %G = %C in DNA.

• Base pairs are stacked with a 36° angle, resulting in 10 base pairs per turn (360°).

• The rise between base pairs is 0.34 Å.

• Major and minor grooves are present in the helix.

Tertiary Structure

• Tertiary structure involves long-range 3D interactions, such as supercoiling and cruciforms.

Semiconservative Nature of DNA Replication

• Each DNA strand serves as a template for a new, complementary strand during replication.

• Three models were proposed: semiconservative, conservative, and dispersive (semiconservative is correct).

Alternative Nucleic Acid Structures

• B-form DNA: Most common in cells.

• A-form DNA: Seen in double-stranded RNA and DNA-RNA hybrids.

DNA and RNA Molecules In Vivo

• DNA can be visualized by electron microscopy.

• DNA exists in relaxed and supercoiled forms; supercoiling is regulated by topoisomerases.

• Gel electrophoresis can separate DNA based on supercoiling and size.

Single-Stranded Polynucleotides

• Most DNA is double-stranded; most RNA is single-stranded.

• Single-stranded nucleic acids can adopt various conformations, including random coils and regions of self-complementarity.

• tRNA has a well-defined tertiary structure due to internal base pairing.

4.4 Alternative Secondary Structures of DNA

Palindromic DNA Sequences: Hairpins and Cruciforms

• Palindromic sequences are symmetrical and can form hairpin or cruciform structures.

Triple-Stranded DNA Structures

• Triple helices can form via Hoogsteen base pairing, often involving self-complementary sequences.

G-Quadruplexes

• G-quadruplexes are four-stranded structures formed by guanine-rich sequences, commonly found in telomeres.

4.5 The Helix-to-Random Coil Transition: Nucleic Acid Denaturation

Denaturation of DNA

• Heating double-stranded DNA separates it into two single strands (denaturation), increasing the energy state.

4.6 The Biological Functions of Nucleic Acids: A Preview of Genetic Biochemistry

Storage and Flow of Genetic Information

• DNA stores the genetic information (genome).

• Replication: DNA is copied for cell division and inheritance.

• Transcription: DNA is transcribed into messenger RNA (mRNA).

• Translation: mRNA is translated into proteins at ribosomes.

Key Enzymes and Processes

• DNA polymerase: Enzyme that synthesizes new DNA strands during replication.

Summary Table: Key Differences Between DNA and RNA

Feature	DNA	RNA
Sugar	Deoxyribose	Ribose
Bases	A, T, G, C	A, U, G, C
Strandedness	Double-stranded	Single-stranded (usually)
Main Function	Genetic information storage	Gene expression, regulation

Additional info: This summary integrates textbook-level explanations and expands on the provided slides for clarity and completeness.