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MOLECULAR BIOLOGY BMS1062

Professor Fasséli Coulibaly
Biomedical Discovery Institute
Department of Biochemistry and Molecular Biology

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DNA as a Blueprint of Life

  • Source:

    • http://www.zo.utexas.edu/faculty/antisense/DownloadfilesToL.html

    • Tree of Life tattoo by Clare D'Alberto, adapted from Life: The Science of Biology, 8th ed. (Sinauer Associates and W. H. Freeman, 2008).

    • Author: Hailey Fournier,

    • Link: https://commons.wikimedia.org/wiki/File:Finalstemcelldifferentiation(1).svg

Molecular Machinery: A Tour of the Protein Data Bank

  • Scale:

    • 1 nm (nanometer) to 10 meters

  • Cellular Locations:

    • Extracellular

    • Membrane

    • Intracellular/Cytosol

    • Intracellular/Nucleus

  • Structure and Function include:

    • DNA

    • Small molecules

    • Digestive Enzymes

    • Blood Plasma

    • Viruses and Antibodies

    • Hormones

    • Channels, Pumps, and Receptors

    • Photosynthesis

    • Energy Production

    • Storage

    • Enzymes and Protein Synthesis

The Central Dogma of Molecular Biology

  • Key Components:

    • Nuclear envelope

    • DNA

    • Pre-mRNA

    • Transcription

    • Translation

    • mRNA

    • Ribosome

    • tRNA

    • Polypeptide

  • Processes:

    • Transcription (RNA synthesis)

    • Processing

    • Translation (protein synthesis)

Learning Outcomes

  • Students should be able to:

    • Demonstrate understanding of primary and secondary structures of DNA and RNA.

    • Explain how DNA acts as a template.

    • Associate DNA structures to functions in storage, replication, and expression of genetic information.

    • Identify four main species of RNAs and their functions in the cell.

Additional Resources

  • Reference:

    • "Structure of Nucleic Acids" Alberts 6th ed, Chapter 4 pp 175-180

    • Useful links:

    • http://biomodel.uah.es/en/model4/dna/index.htm

    • http://pdb101.rcsb.org/motm/23

    • http://www.wehi.edu.au/wehi-tv/molecular-visualisations-dna

    • YouTube link: https://www.youtube.com/watch?v=o_-6JXLYS-k&feature=youtu.be

    • https://history.nih.gov/exhibits/nirenberg/HS2_DNA.htm

A Brief History of DNA

  • 1866: Gregor Mendel lays the groundwork for genetics.

  • 1869: DNA first isolated by Friedrich Miescher.

    • Studied white blood cells, identified a phosphorus-rich material termed nuclein.

  • 1944: Oswald Avery's experiments identify DNA as genetic material.

  • 1953: Watson and Crick propose the double-helix structure of DNA using X-ray diffraction data from Rosalind Franklin and Maurice Wilkins.

  • 2001: Human genome sequenced.

The Structure of Nucleic Acids

  • Nucleotides

    • DNA and RNA are polymers of nucleotides.

  • Components of the Names:

    • D/R: Deoxyribose/Ribose

    • N: Nucleic acids derived from the nucleus.

    • A: Acidic properties (negatively charged at physiological pH).

Nitrogenous Bases

  • Purines:

    • Double carbon/nitrogen ring

  • Pyrimidines:

    • Single carbon/nitrogen ring

  • Unique bases:

    • Uracil (in RNA)

    • Thymine (in DNA)

Sugars and Nucleotides

  • Nucleotide structure comprises:

    1. Base

    2. Sugar

    3. Phosphate group

  • Base + Sugar = Nucleoside

  • Base + Sugar + Phosphate = Nucleotide

  • Types of sugars used:

    • B-D-ribose (used in RNA)

    • B-D-2-deoxyribose (used in DNA)

Structural Features of DNA

  • Four key features:

    • Minor and major grooves

    • Uniform diameter of 2 nm in B-form

    • Right-handed twist with 10-10.5 base pairs per turn

    • Antiparallel orientation

Complementary Base Pairing

  • Hydrogen Bonding:

    • A–T: Two hydrogen bonds

    • C–G: Three hydrogen bonds

  • Law of Complementary Base Pairing:

    • The sequence of one strand determines the base sequence of the other.

Functions of DNA

  • Storage of genetic information

  • Precise copying required for cell division

  • Must be readable for gene expression

  • Susceptible to mutations

Structural Implications of DNA

  • Two complementary strands

  • Each strand serves as a template for replication and repair

DNA in Prokaryotic Cells

  • Prokaryotic DNA is typically circular, supercoiled, and associated with an RNA-protein core.

Chromatin Structure

  • DNA is packed into mitotic chromosomes through nucleosomes

  • Nucleosome structure:

    • 147 bp + 8 histone proteins

General Features of RNA Structure

  • Four bases: A, C, G, U

  • Single stranded

  • Functions include mRNA, tRNA, rRNA, and other types

Types of RNA

  • Major species include:

    • mRNA: Messenger RNA, codes for proteins

    • rRNA: Ribosomal RNA, key structural component of ribosomes

    • tRNA: Transfer RNA, matches mRNA codons to amino acids

  • Other RNA types include:

    • snRNA, snoRNA, miRNA, siRNA, piRNA, lncRNA

RNA Structures

  • Normally single-stranded but with complex secondary and tertiary structures, such as hairpins and loops.