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).

Types of Nucleic Acids: DNA and RNA

• DNA contains deoxyribose sugar and is the genetic material in most organisms.

• RNA contains ribose sugar and plays roles in gene expression and protein synthesis.

• Both are polymers of nucleotides, which consist of a sugar, a phosphate group, and a nitrogenous base.

Nitrogenous Bases

• Pyrimidines: Cytosine (C), Thymine (T, in DNA), and Uracil (U, in RNA)

• Purines: Adenine (A) and Guanine (G)

• DNA contains A, G, C, T; RNA contains A, G, C, U.

Nucleosides and Nucleotides

• Nucleoside: Nitrogenous base + sugar

• Nucleotide: Nucleoside + phosphate group

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

Properties of Nucleotides

• Acidity: Nucleotides are strong acids due to phosphate ionization.

• Tautomerization: Bases can exist in different tautomeric forms (amino/imino, keto/enol), affecting base pairing.

• UV Absorption: Nucleotides absorb UV light at ~260 nm, a property used to detect and quantify nucleic acids.

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.

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

4.3 Secondary and Tertiary Structures of Nucleic Acids

Secondary Structure: The DNA Double Helix

• Secondary structure refers to the 3D arrangement of nucleotides, such as the double helix in DNA.

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

• Base pairing: A pairs with T (or U in RNA), G pairs with C (Chargaff's rules: %A = %T, %G = %C).

• 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.

• The double helix has major and minor grooves important for protein binding.

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; the semiconservative model 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

Genetic Information Flow

• 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.

• Transcription: The process of synthesizing RNA from a DNA template.

• Translation: The process of synthesizing proteins from mRNA templates.

Table: Comparison of DNA and RNA

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

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