SPS 205: Biochemistry III - Nucleic Acids

SPS 205: BIOCHEMISTRY III

• Course Lecturer: Nsoh Godwin Anabire
• Department of Biochemistry and Molecular Medicine, School of Medicine
• University for Development Studies, Tamale
• Email: [email protected], [email protected]

Lecture 2: Structure and Function of Nucleic Acids

• Science should be as simple as possible, but not simpler - Albert Einstein
• Course content revolves around molecular genetics
• Topics include:
  • Nucleic acid structures
  • Nucleotide metabolism
  • DNA synthesis
  • DNA damage and repair
  • Transcription and its regulation
  • Post-transcriptional RNA modifications
  • Translation (co- and post-translational modifications)
  • Biotechnology (processes of isolation and analysis of DNA)

Nucleus

• Largest organelle in animal cells
• Contains a dense compartment (nucleolus) where ribosomal RNA is synthesised
• DNA is distributed along multiple long linear structures (chromosomes)
• Euchromatin: Uncoiled, loosely packed chromatin; genetically active
• Heterochromatin: Condensed, concentrated chromatin; cannot be transcribed into RNA

Definition of Some Terms (1)

• Chromatin: Complex of DNA, histones, and non-histones found in the eukaryotic cell nucleus.
• Histones: Group of small, abundant proteins rich in arginine and lysine; form nucleosome cores
• Chromosome: Structure made of a long DNA molecule and associated proteins carrying hereditary information.
• Chromatid: One of the two copies of a duplicated chromosome formed during DNA replication in S-phase.

Definition of Some Terms (2)

• Gene: Region of DNA that is transcribed as a single unit and carries information for a discrete hereditary characteristic.
• Usually corresponds to:
  • A single protein (or set of related proteins generated by variant post-translational processing)
  • A single RNA (or set of closely related RNAs)
• Genome: Totality of genetic information belonging to a cell or organism; specifically, the DNA carrying this information.

Overview of Four Basic Molecular Genetic Processes

• Processes: Replication, Transcription, RNA-processing, and Translation. Diagram outlining the process, showing the players in the mechanism and where in the cell the mechanisms take place are detailed within a visual aid.

Organization of Chromatin

• Visual illustration of Chromatin's structure from the double helix to the chromosome.
  • Key terms & measurements included: DNA double helix (2 nm), Nucleosome (10 nm), Solenoid (30 nm), Loops (200-700 nm), Chromosome (700 nm), Nuclear Scaffold.

Nucleic Acids

• Defined as molecules (polymers of nucleotides) responsible for organism characteristics.
• Two types: Ribonucleic acid (RNA) and Deoxyribonucleic acid (DNA).

Nucleic Acids-Overview

• Play a central role in genetic information storage and expression.
• Divided into two major classes: Deoxyribonucleic acid (DNA) for information storage and Ribonucleic acids (RNAs) involved in gene expression and protein biosynthesis.
• All nucleic acids are composed of nucleotide components (base, sugar, phosphate residue).
• DNA and RNA differ in the sugar and one base type.

Nucleic Acids-Nitrogenous Bases

• Bases in nucleic acids are aromatic heterocyclic compounds (derived from pyrimidine or purine).
• Five bases are main components of nucleic acids in all living creatures.
  • Purines: Adenine (A) and Guanine (G)
  • Pyrimidine: Cytosine (C); Uracil (U) found in RNA.
  • Thymine (T) in DNA, a 5-methyl derivative of uracil.

Definitions- Pyrimidine

• Aromatic heterocyclic organic compounds with a single six-membered ring.
• First and third atoms are nitrogen, rest are carbon.
• Include: Cytosine, Thymine, and Uracil.

Definitions- Purine

• Heterocyclic aromatic organic compounds with two rings.
• Include: Adenine and Guanine

Nucleoside

• Formed when a nucleic acid base is N-glycosidically linked to ribose or deoxyribose.
• Examples: Adenosine, guanosine, uridine, thymidine, and cytidine.
• Deoxyribonucleosides are formed when the sugar is 2-deoxyribose, such as 2-deoxyadenosine.

Nucleoside structure-Adenosine as an example

• Sugars and bases are linked by an N-glycosidic bond.
• Bond connects the C-1 of the sugar to N-9 of the purine ring or N-1 of the pyrimidine ring.
• Bond always adopts the β-configuration.

Nucleotides

• 5' OH group of the nucleoside is esterified with phosphoric acid.
• Examples include: 2'-deoxythymidine-5'-monophosphate (dTMP).
• Nucleotide formation results from an acid-anhydride bond linking 5-phosphate to additional phosphate residues.
• Examples include ADP and ATP (important coenzymes in energy metabolism).

Nucleotides structure-dTMP as an example

• Diagram showing the structure of dTMP, a specific nucleotide.

Nomenclature of bases, nucleosides, and nucleotides

• Table providing the names of bases, their corresponding nucleosides and nucleotides (e.g., Adenine to Adenosine 5'‐monophosphate).

Nucleic Acid- in summary

• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA)
• Nucleic acids are polynucleotides
• Their building blocks are nucleotides

Nucleotide Structure

• Diagram detailing the structure of nucleotides, showing:
  • Phosphate group
  • Sugar (ribose or deoxyribose)
  • Base (purine or pyrimidine)

Nucleic Acid polymerization (1)

• Phosphate residue of one nucleotide reacts with the 3'-OH group of an adjacent nucleotide.
• Resulting in a dinucleotide with a phosphoric acid diester bond.
• Dinucleotides extend via additional mononucleotides forming oligonucleotides and polynucleotides.

Nucleic Acid polymerization (1)

• Polynucleotides consisting of deoxyribonucleotides = DNA
• While consisting of ribonucleotides = RNA
• Structure of polynucleotides is described with abbreviations for nucleoside components from 5' → 3` direction.

Nucleic acid structure cont.

• DNA's double helix structure has two nucleotide strands running in opposite directions.
• Bases are arranged in pairs (A-T and G-C) held together by hydrogen bonds.
• Complimentary base pairing (A-T, G-C) is specific (2 hydrogen bonds for A-T, 3 hydrogen bonds for G-C)
• Each base pair is a purine paired with a pyrimidine.

DNA Structure

• Diagrams illustrating the visual representation of DNA structure, including examples of base pairs.

Four types of interactions affecting double-stranded DNA conformation

• Stacking interactions
• Hydrogen bonds
• Hydrophobic effects
• Charge-charge interactions (Electrostatic)

This quiz covers the structure and function of nucleic acids, focusing on molecular genetics. Topics include DNA synthesis, repair, transcription regulation, and various modifications in translation. Test your knowledge on key concepts and processes in biochemistry.