5.1 - DNA Structure and Organization in the Cell

DNA Structure and Organization in the Cell

Pages 204-218 (McGraw-Hill Ryerson, 2011)

Subtopics

  • Identifying DNA as the Material of Heredity

    • Griffith - Transformation; supported by Avery et al.

    • Hershey and Chase - DNA is the Genetic Material

  • Determining the Chemical Composition and Structure of DNA

    • Levene; Chargaff - Composition/Structure

  • Determining the Three-Dimensional Structure of DNA

    • Watson/Crick/Pauling/Franklin - 3D Structure (Double Helix)

  • The Structure and Organization of Genetic Material in:

    • Prokaryotes and Eukaryotes

Identifying DNA as the Material of Heredity

  • Historical Context: 1928, London, England

    • Bacterial pneumonia, a significant cause of fatalities globally.

Griffith's Experiment

  • Frederick Griffith (1928):

    • Microbiologist who discovered a "transforming principle" that could be transferred between organisms.

    • Inspired Avery, MacLeod, and McCarty to investigate the nature of this substance.

Key Discoveries by Avery et al.

  • Oswald Avery, Colin MacLeod, Maclyn McCarty (1944):

    • Established DNA as the transforming principle through isolation and chemical characterization.

    • Challenged the belief that proteins were the hereditary molecules.

Hershey and Chase Experiment

  • Alfred Hershey & Martha Chase (1952):

    • Utilized T2 bacteriophage and radioisotopes of sulfur (for proteins) and phosphorus (for DNA) to track substance transfer.

    • Confirmed that DNA was the hereditary material by ruling out proteins.

Determining Chemical Composition of DNA

  • Friedrich Miescher (1869-1871):

    • Extracted a weakly acidic substance from cell nuclei, identified as nuclein (later known as nucleic acid).

Contributions from Phoebus Levene

  • Identified ribose (1909) and deoxyribose (1929) as sugar components of nucleic acids.

  • Determined the structure of nucleotides as monomers of nucleic acids, composed of:

    • Sugar

    • Phosphate

    • One of four nitrogenous bases

Nitrogenous Bases

  • Pyrimidines:

    • Cytosine (C)

    • Thymine (T, in DNA)

    • Uracil (U, in RNA)

  • Purines:

    • Adenine (A)

    • Guanine (G)

Chargaff's Rule

  • Erwin Chargaff (1944-1950):

    • Discovered that the amounts of adenine (A) is equal to thymine (T), and cytosine (C) to guanine (G).

    • Established that DNA composition varies among species, which laid the foundation for understanding DNA's role in heredity.

Three-Dimensional Structure of DNA

  • Consolidated knowledge:

    • Hershey and Chase affirming DNA as hereditary material.

    • Levene confirming nucleotide structure.

    • Chargaff’s variations in nucleotide proportions.

Watson and Crick's Contributions

  • James Watson (Biologist) & Francis Crick (Physicist):

    • Aimed to uncover the three-dimensional structure of DNA, relying on Franklin's x-ray diffraction data and Pauling's molecular model insights.

Linus Pauling and Rosalind Franklin

  • Linus Pauling:

    • Nobel Laureate who characterized molecular diseases, instrumental in understanding molecular biology and 3D molecular shapes.

  • Rosalind Franklin:

    • Expert in x-ray crystallography, her images revealed a helical structure and dimensions of DNA.

    • Proposed that DNA forms a double helix with interior base pairs and an exterior sugar-phosphate backbone.

Watson and Crick's Proposal

  • Initially suggested an incorrect structure with exterior base pairs but corrected this view after seeing Franklin’s diffraction images, leading to understanding the anti-parallel strands of DNA.

Modern DNA Model

  • DNA Double Helix:

    • Composed of two polynucleotide strands that coil around each other.

    • Complementary strands are held together by hydrogen bonds between nitrogenous bases (A-T and C-G pairing).

    • Strands run in opposite directions (5'-3' vs. 3'-5').

Genetic Material Organization

Prokaryotes

  • Genome:

    • Circular double-stranded DNA

    • Multiple copies of one chromosome, nucleoid without membrane.

    • DNA is compacted through supercoiling, utilizing proteins and enzymes such as topoisomerases.

    • Some possess plasmids, which are small DNA circles that can transfer between cells.

Eukaryotes

  • More complex genomes:

    • Extensive DNA compacting via histones forming nucleosomes.

    • Chromatin is the non-condensed form predominating during interphase.

    • Nucleosomes consist of DNA wrapped around histone proteins, affecting gene regulation.

    • Eukaryotic genome shows variation across haploid, diploid, triploid, and polyploid organisms.

    • Gene organization can change in location, spacing, and number on chromosomes, indicating complexity not purely defined by gene quantity.