DNA Structure & Chromosomal Organisation

Week 6: DNA Structure & Chromosomal Organization

• Overview of Key Terms:
  • Cell: Basic unit of life.
  • Nucleus: Organelle that contains DNA.
  • Base pair: Two nucleotides bound together by hydrogen bonds.
  • Chromosome: Structure of tightly coiled DNA.
  • DNA (Double Helix): The helical structure of DNA.
  • Histone proteins: Proteins that package and order DNA into structural units called nucleosomes.
  • Nucleosomes: DNA wrapped around histone proteins.

DNA Discovery: Humble Beginnings

• Friedrich Miescher (1860s): First to purify nuclei from pus cells.

  • Extracted a substance named nuclein composed of Hydrogen, Carbon, Oxygen, Nitrogen, and Phosphorous.

• Early 1900s: Chromosomes recognized for carrying genetic information containing both DNA and proteins (20 amino acids).

Transformation Experiment

• Frederick Griffith: Notable experiments using Streptococcus pneumoniae strains.

  • Strain S (with capsule): Causes infection.
  • Strain R (no capsule): No infection.
  • Mice injected with live S strain died; live R strain did not cause death.

• Heat-killed S strain + live R strain: Mice died, indicating transformation occurred - genetic information passed from dead S strain to live R strain.

Nucleic Acids as Genetic Material

• Avery, MacLeod & McCarty (1944): Proved nucleic acids, not proteins, are genetic material.

• Hershey & Chase (1952): Used bacteriophages to prove DNA carries genetic information.

  • Radioactive tracers used to trace whether proteins or DNA entered bacterial cells.

Nucleic Acid Structure

• Types of Nucleic Acids:

  • DNA (Deoxyribonucleic acid): Double-stranded, contains A, T, C, G.
  • RNA (Ribonucleic acid): Single-stranded, contains A, U, C, G.

• Nucleotide Structure:

  • Consists of a phosphate group, sugar (deoxyribose in DNA, ribose in RNA), and nitrogen-containing bases (purines: A and G; pyrimidines: C and T/U).

Chargaff’s Rules

• Equal quantities of adenine (A) and thymine (T); cytosine (C) and guanine (G).
• Total purines (A + G) equal total pyrimidines (C + T).

Rosalind Franklin

• Conducted X-ray crystallography studies indicating:
  • DNA is a helix, phosphates on the exterior, and has a consistent diameter.

Watson and Crick Model

• Proposed structure of DNA in 1953:
  • Two antiparallel chains of nucleotides forming a double helix with complementary base pairing (A-T, C-G).
• Genetic information is stored in the sequence of bases.
• DNA is compacted into tightly coiled chromosomes in the nucleus.

DNA Replication

• Semi-conservative Replication: Each daughter DNA molecule contains one old strand and one new strand.
• Key Enzymes:
  • Helicase: Unwinds the DNA helix.
  • Primase: Synthesizes RNA primer for DNA polymerase.
  • DNA Polymerase III: Synthesizes the new DNA strand, adding nucleotides in a 5’ to 3’ direction.
  • Ligase: Joins Okazaki fragments on the lagging strand.

Chromosome Organization

• Each chromosome made up of highly coiled double-stranded DNA.
• Nucleosomes formed by DNA winding around histones, condensing DNA significantly.
• Centromere: Region where sister chromatids attach; forms kinetochores during cell division.
• Telomeres: Repetitive DNA sequences that protect chromosome ends; shorten with cell division but are restored in germ cells by telomerase.

Summary

• DNA is essential for genetic information storage and transmission.
• Replication is semi-conservative and involves several critical enzymes ensuring accuracy.
• Chromosomes organize DNA into a compact structure necessary for cell division and functionality.