Lecture on DNA Structure and Replication

Introduction to DNA

• DNA is composed of nucleotides, specifically deoxyribonucleotides.
• Backbone: Phosphate group attached to a five-carbon sugar called deoxyribose.
• Nitrogenous Bases: Adenine (A), Thymine (T), Guanine (G), Cytosine (C).
• Nucleotides are linked by phosphodiester bonds.
• DNA has directionality: Read from 5' to 3'.

Historical Background

• Pre-1950s, DNA known as the genetic code but structure was unknown.
• James Watson and Francis Crick identified DNA structure in 1953.
• Rosalind Franklin's photography provided critical insights to Watson and Crick without her knowledge.
• Watson and Crick proposed the double helix structure and anti-parallel strands of DNA.

DNA Structure

• Two strands of DNA are anti-parallel, meaning they run in opposite directions.
• Pairing of bases is complementary: A pairs with T, and G pairs with C.
• Discovery led to understanding of DNA replication.

DNA Replication Theories

• Semiconservative Replication: Each strand serves as a template, resulting in new double-stranded DNA with one parental and one new strand.
• Conservative Replication: Parental DNA is copied entirely, resulting in one fully parental and one fully new DNA molecule.
• Dispersive Replication: DNA molecules are hybrid of parental and new DNA.

Meselson-Stahl Experiment

• Used nitrogen isotopes (N-14 and N-15) to track DNA replication in E. coli.
• Data supported semiconservative replication: New DNA molecules contained one old and one new strand.

Mechanism of DNA Replication

• Initiation: DNA helicase unwinds the double helix, stabilized by single-strand binding proteins.
• Elongation: DNA polymerase adds nucleotides in 5' to 3' direction.
  • Leading strand: Synthesized continuously toward replication fork.
  • Lagging strand: Synthesized in Okazaki fragments, away from replication fork.
• Termination: DNA ligase joins Okazaki fragments.

Additional Insights into DNA Replication

• Replication bubbles form and synthesis occurs bidirectionally.
• Bacteria have single origin of replication; eukaryotes have multiple.
• Telomeres and telomerase protect chromosome ends from shortening during replication.

Accuracy and Mutation

• DNA replication is highly accurate with built-in proofreading by DNA polymerase III.
• Repair enzymes correct mismatched bases.
• Mutations occur but can sometimes confer evolutionary advantages.

Summary

• DNA replication is crucial for cell division and genetic continuity.
• Fundamental understanding comes from studies in E. coli bacteria.
• Overall process involves initiation, elongation, and termination with a high degree of fidelity.