Nucleic Acids: Structure, Properties, and Biological Functions

4.1 Nucleic Acids – Informational Macromolecules

Introduction to Nucleic Acids

• Nucleic acids are large biomolecules essential for all known forms of life, serving as the carriers of genetic information.

• There are two main types: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

Chemical Structures of DNA and RNA

• Both DNA and RNA are polymers of nucleotides, but differ in their sugar component and one of their bases.

• DNA contains deoxyribose sugar, while RNA contains ribose sugar.

• DNA uses thymine (T) as a base, whereas RNA uses uracil (U).

Pyrimidine and Purine Bases

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

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

• These bases pair specifically (A with T/U, G with C) to encode genetic information.

Nucleosides and Nucleotides

• Nucleoside: Base + sugar (ribose or deoxyribose).

• Nucleotide: Nucleoside + phosphate group(s).

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

Properties of Nucleotides

• Nucleotides are strong acids due to their phosphate groups.

• Phosphate groups can ionize at different pH values, affecting nucleotide charge.

• Bases can exist in different tautomeric forms (e.g., keto/enol, amino/imino), influencing base pairing.

• Nucleotides absorb ultraviolet (UV) light maximally at around 260 nm, a property used to 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.

• This linkage forms the backbone of DNA and RNA strands.

• Nucleic acid synthesis requires 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').

• This sequence encodes genetic information.

4.3 Secondary and Tertiary Structures of Nucleic Acids

The DNA Double Helix

• The secondary structure refers to the three-dimensional arrangement of nucleotide residues, such as the double helix in DNA.

• The tertiary structure involves longer-range 3D interactions, including supercoiling and complex folding.

Key Features of the DNA Double Helix

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

• Bases pair via hydrogen bonds: A with T (or U in RNA), G with C (Chargaff's rules: %A = %T, %G = %C).

• Bases are stacked with a 36° angle between pairs, 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.

Semiconservative Nature of DNA Replication

• During replication, each DNA strand serves as a template for a new complementary strand.

• This is known as semiconservative replication.

• Three models were proposed: semiconservative, conservative, and dispersive; experiments confirmed the semiconservative model.

Alternative Nucleic Acid Structures: B and A Helices

• The B form is the most common DNA structure in cells.

• The A form is found in double-stranded RNA and DNA-RNA hybrids.

DNA and RNA Molecules In Vivo

• DNA can be visualized by electron microscopy, revealing relaxed and supercoiled forms.

• Supercoiling is regulated by enzymes called topoisomerases.

• Gel electrophoresis can separate DNA molecules based on their degree of supercoiling; more compact forms migrate faster.

Single-Stranded Polynucleotides

• Most DNA is double-stranded, but most RNA is single-stranded.

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

• Transfer RNA (tRNA) has a well-defined tertiary structure due to extensive intramolecular 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

• DNA can form triple helices via Hoogsteen base pairing, often in regions with homopurine-homopyrimidine stretches.

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 causes denaturation, separating it into two single strands.

• This process is reversible; cooling allows renaturation (reannealing) of the strands.

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) of an organism.

• Replication ensures genetic information is passed from cell to cell and generation to generation.

• Transcription converts DNA information into messenger RNA (mRNA).

• Translation uses mRNA to direct protein synthesis at ribosomes.

Replication and the DNA Polymerase Reaction

• DNA polymerase is the enzyme responsible for synthesizing new DNA strands during replication.

• It is part of a larger complex called the replisome.

Transcription and Translation

• During transcription, a segment of DNA is used as a template to synthesize RNA.

• During translation, the sequence of nucleotides in mRNA is used to assemble amino acids into a protein.

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 (usually)	Single-stranded (usually)
Main Function	Genetic information storage	Information transfer and protein synthesis

Additional info: The notes above expand on the provided slides by including definitions, explanations of tautomerization, and the biological significance of nucleic acid structures and processes. The summary table is inferred for clarity and exam preparation.