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).
- Phosphate group
- Pentose sugar
- 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:
- 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.