Nucleic Acids Structure and Function

Nucleic Acids: Structure and Function

• Nucleic acids are composed of nucleotide building blocks (polynucleotides).
• Two types: ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).
• Each nucleotide has a base, a sugar, and one or more phosphate groups.

DNA Structure & Replication

• DNA is the cell's informational store, determining protein synthesis timing and method.
• Proteins: Major cell players, including enzymes that regulate reaction rates (e.g., lipid and carbohydrate synthesis/breakdown) and structural proteins shaping cells and influencing cell-cell communication (e.g., peptide hormones, cell adhesion).
• DNA replication: A semi-conservative process where each strand serves as a template, producing two identical DNA molecules, each with one original and one newly synthesized strand.
• Replication is bidirectional, often with multiple origins, making it efficient for a large eukaryotic genome.
• DNA synthesis occurs in the 5' to 3' direction.

Eukaryotic Genome

• The eukaryotic genome is the complete set of genetic information within a eukaryotic cell.
• This information dictates daily cellular functions and responses to cellular stress conditions.
• Most of the genome (approximately 30,000 genes) is located in the cell's nucleus, with some genes residing in the mitochondria - both maternal and paternal origins.

Physical Organisation

• The genome is compartmentalized within two primary parts: the nucleus and mitochondria.
• The bulk of the genome resides within chromatin, organized into chromosomes.
• Human cells contain 23 pairs of chromosomes.

Data Storage Analogy

• Nucleic acids store genetic information similarly to libraries storing books.
• Letters -> Nucleotides
• Words -> Motifs
• Sentences -> Genes
• Paragraphs -> Chapters
• Books -> Chromosomes
• Shelves -> Nucleus
• Bookcases -> Cell
• Library -> Genome

Why are Nucleic Acids Important?

• DNA stores cellular information, dictating protein production.
• Proteins are key players within the cell; enzymes regulating reaction rates and structural proteins shaping cells.

Central Dogma of Molecular Biology

• The central dogma describes the unidirectional flow of genetic information: DNA replicates to DNA; DNA transcribes to RNA; RNA translates to protein.

Structure of Nucleotides

• Nucleotides are composed of a base, a sugar (ribose in RNA, deoxyribose in DNA), and one or more phosphate groups.
• There are five bases: adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U). A, C, G are found in both RNA and DNA. A and T are only found in DNA and A and U are only found in RNA.

Sugars (Monosaccharides)

• The sugars in DNA and RNA are pentoses (five-carbon sugars): ribose in RNA and deoxyribose in DNA.
• Deoxyribose differs from ribose by the absence of an oxygen atom at the 2' carbon position

Phosphates

• Phosphates form the backbone of nucleic acids' structure.
• They can exist as mono-, di-, or tri-phosphates.
• Examples include AMP (adenosine monophosphate), ADP (adenosine diphosphate), ATP (adenosine triphosphate).

Nucleic Acid Structure

• Nucleotides connect through 3'-5' phosphodiester linkages (covalent bonds).
• Nucleic acids have a directional 5' to 3' orientation.
• Base sequences in nucleic acids are not restricted.

Base Pairing

• Bases interact through hydrogen bonds in base pairing, a crucial step in DNA replication and transcription.
• A pairs with T or U (2 hydrogen bonds); G pairs with C (3 hydrogen bonds) .
• This specificity allows for accurate information transfer between DNA and RNA.

DNA is a Double Helix

• DNA exists as a double helix, with two strands coiled around a common axis.
• There are about 10 base pairs per turn in the helix.
• The human genome contains approximately 3.2 billion base pairs.

Chemical Structure of dsDNA

• DNA strands run in opposite directions (antiparallel).
• A pairs with T, and G pairs with C.

DNA Replication

• A process where pre-existing DNA sequences facilitate the creation of new DNA strand sequences through specific chemical interactions.

Replication Fork

• The replication fork is the point where DNA strands separate during replication.
• The leading strand is synthesized continuously, while the lagging strand is synthesized discontinuously in short fragments (Okazaki fragments).
• Okazaki fragments are connected by DNA ligase.

RNA Primer

• A short RNA sequence initiates DNA synthesis on the lagging strand.
• Primase is the enzyme that synthesizes RNA primers.

DNA Helicases

• Enzymes that unwind the DNA double helix ahead of the replication fork.

Topoisomerases

• Enzymes that relieve the torsional stress on DNA during unwinding and replication.
• They prevent DNA breaking.
• Some bacterial DNA gyrases are targeted by antimicrobial agents.
• Some human topoisomerases are targeted by anticancer agents.

DNA Ligase

• Enzyme that joins Okazaki fragments.

DNA Polymerases

• Enzymes that catalyze the addition of nucleotides to the 3' end of a growing DNA strand.
• Several DNA polymerases (e.g. Pol α, Pol δ, Pol ε, Pol γ) have specific functions in eukaryotic cells. Pol α often has primase activity.

Eukaryotic Cell Cycle

• The eukaryotic cell cycle is a series of events that lead to cell division.
• It includes phases such as G1, S, G2, and M (mitosis or meiosis).
• The S phase involves DNA replication.

Telomeres

• Repetitive DNA sequences at the ends of eukaryotic chromosomes.
• Protective caps that shorten with each cell division.

Telomere Repeats

• Specific DNA sequences at chromosome ends.
• The sequence (TTAGGG)n protects the end of the chromosome.

Telomerase

• Enzyme that maintains telomere length, which is crucial for preventing chromosome shortening.

Medical Relevance of Telomeres

• Telomere shortening impacts normal somatic cell division while cancer and stem cells have unlimited division abilities.
• Telomere shortening is a key factor in aging.

Related Pharmacology

• DNA synthesis inhibitors, such as AZT and cytosine arabinoside, are nucleoside analogs that interfere with DNA replication.

Causes of DNA Damage

• DNA damage can result from environmental agents (chemicals, UV radiation).
• Errors during replication can cause DNA damage.
• Normal chemical changes can also cause damage.
• Mutations are heritable changes in DNA sequences that alter genetic information permanently.

Explore the fascinating world of nucleic acids, including the structure and function of DNA and RNA. This quiz covers key concepts such as nucleotides, DNA replication, and the role of proteins in cellular processes. Test your knowledge on the essential building blocks of life!