A Closer Look at DNA: DNA Structure and Replication

History

• James Watson and Francis Crick (1953):
  • Determined the structure of DNA.
  • Rosalind Franklin contributed through X-ray crystallography.

Structure of DNA

• Nucleotides: Building blocks of DNA (and RNA).
  • Components:
  1. Phosphate group
  2. Pentose sugar
  3. Nitrogenous base
• Double Helix:
  • Two strands form a ladder-like structure.
  • Backbone: Sugar-phosphate.
  • Rungs: Nitrogenous bases.
    • Purines: Guanine (G), Adenine (A).
    • Pyrimidines: Cytosine (C), Thymine (T).
• Key Features:
  • Antiparallel strands.
  • Hydrogen bonds connect bases.
  • Covalent bonds link the backbone.
• Conventional Numbering System:
  • Sugar carbons numbered 1' to 5'.
  • Base attached to 1', phosphate attached to 5'.

Facts about DNA

• Human Genome:
  • Each cell contains 46 DNA molecules (one double helix per chromosome).
  • Total of 6 billion base pairs in humans.
  • Stretched DNA: 5 feet long, 50 trillionths of an inch wide.
  • Human genome contains 3,164.7 million chemical nucleotide bases.
• Genes & Estimates:
  • Average gene: 3000 bases; largest gene (dystrophin): 2.4 million bases.
  • Estimated number of genes: 30,000 (much lower than previous estimates of 80,000 - 140,000).
  • 99.9% of nucleotide bases are identical in all humans.
  • Functions of over 50% of genes are unknown.
  • Less than 2% of genome codes for proteins.
  • "Junk DNA" (non-coding sequences) constitutes at least 50% of genome.
  • The order of bases determines species identity.
• Genomics: Study of genomes.
• DNA replication errors: 1 error per 10 billion nucleotides.

DNA Replication

• Models of Replication (1950s):
  • Semiconservative
  • Conservative
  • Dispersive
• Key Terms:
  • Daughter strands: Newly made strands.
  • Parental strands: Original strands.
• Process:
  • Begins at origin points (replication bubbles and forks).
  • Parental strands separate, serve as templates.
  • Follow A-T / G-C base pairing rules.
  • Result: 2 new double helices with identical base sequences.
• Directionality:
  • Synthesis proceeds 5' to 3'.
  • Leading strand synthesized continuously in direction of fork.
  • Lagging strand synthesized in Okazaki fragments.

Enzymatic Proteins in DNA Replication

• DNA Polymerase:
  • Catalyzes elongation of new DNA.
  • Cannot initiate synthesis on an empty template strand.
  • Requires RNA primer from DNA primase.
• Primase:
  • Synthesizes short RNA primers (5-10 nucleotides).
• DNA Ligase:
  • Joins Okazaki fragments.
• DNA Helicase:
  • Binds to DNA, unwinds strands using ATP.
• DNA Topoisomerase:
  • Relieves strain ahead of replication fork.
• Single-Strand Binding Proteins:
  • Keep parental strands open during replication.

Telomeres and DNA Repair

• DNA Repair:
  • Enzymes like DNA polymerase help repair damage.
• Telomeres:
  • Non-repairable regions of DNA.
  • Composed of repeating sequences (TTAGGG).
• Function of Telomeres:
  • Protect genes from erosion during cell division.
• Telomerase:
  • Enzyme that counters telomere shortening.
  • Active in gamete-producing cells and cancer cells.
  • Discovered by Carol Greider and Elizabeth Blackburn in 1984.