Chapter 13: Molecular Basis of Inheritance

Overview: Life’s Operating Instructions

The discovery of DNA's structure revolutionized our understanding of heredity. DNA contains the instructions for the development and functioning of all living organisms, and its accurate replication is essential for life.

• Double-Helical Model: Introduced by James Watson and Francis Crick in 1953, based on data from multiple researchers.

• Hereditary Information: DNA directs biochemical, anatomical, physiological, and some behavioral traits.

• DNA Replication: Ensures all cells inherit identical genetic information.

13.1 DNA is the Genetic Material

Evidence for DNA as Genetic Material

DNA is a polymer composed of nucleotides, each containing a nitrogenous base, a pentose sugar (deoxyribose), and a phosphate group. Multiple lines of evidence established DNA as the molecule of heredity.

• Nitrogenous Bases: Adenine (A), Guanine (G), Thymine (T), Cytosine (C).

• Chargaff’s Rules:

  • DNA base composition varies between species.

  • Within a species, %A = %T and %G = %C.

  • Purines (A, G) pair with pyrimidines (T, C), resulting in uniform width of DNA.

Building the Structural Model of DNA

The structure of DNA was determined through scientific inquiry and collaboration.

• Rosalind Franklin: Used X-ray crystallography to reveal DNA’s helical structure, major and minor grooves, and uniform width.

• Watson and Crick: Used Franklin’s data and Chargaff’s rules to propose the double helix model.

• Antiparallel Strands: Sugar-phosphate backbones run in opposite directions (5’ to 3’).

• Base Pairing: A pairs with T, C pairs with G via hydrogen bonds.

13.2 Many Proteins Work Together in DNA Replication & Repair

Base Pairing to a Template Strand

DNA replication relies on the complementarity of the two strands. Each strand serves as a template for the synthesis of a new strand, ensuring genetic fidelity.

• Semiconservative Replication: Each new DNA molecule contains one old strand and one new strand.

• Parent DNA: Unwinds to allow daughter strands to be built.

DNA Replication: A Closer Look

Replication is a highly accurate and rapid process, involving many enzymes and proteins. The basic mechanism is similar in prokaryotes and eukaryotes, though details differ.

• Origins of Replication:

  • Prokaryotes: Single origin on circular chromosome, two replication forks.

  • Eukaryotes: Multiple origins on linear chromosomes, many replication forks.

• Replication Bubbles: Form at origins, forks move in opposite directions.

Initiation of DNA Replication: Key Enzymes

• Helicase: Untwists and separates DNA strands at replication forks.

• Single-Strand Binding Proteins: Stabilize separated strands.

• Topoisomerase: Relieves strain ahead of replication fork by cutting and rejoining DNA.

Synthesizing a New Strand

DNA polymerases can only add nucleotides to an existing chain, so replication begins with an RNA primer.

• Primase: Synthesizes short RNA primers (~5–10 nucleotides).

• DNA Polymerases:

  • Add nucleotides to the 3’ end of the primer.

  • Proofread and ensure correct base pairing.

  • Elongation rate: 500 nucleotides/sec (bacteria), 50 nucleotides/sec (humans).

  • Form phosphodiester bonds via dehydration synthesis.

• RNA Primer Removal: Replaced by DNA nucleotides.

Antiparallel Elongation

DNA strands are synthesized in opposite directions due to their antiparallel nature.

• Leading Strand: Synthesized continuously toward the replication fork; requires one primer.

• Lagging Strand: Synthesized discontinuously away from the fork in short segments called Okazaki fragments.

• DNA Ligase: Joins Okazaki fragments to form a continuous strand.

Proofreading and Repairing DNA

Accurate DNA replication is vital for cell survival. Multiple mechanisms ensure fidelity and repair damage.

• Proofreading: DNA polymerases correct errors during replication (error rate: 1 in 10 billion).

• Mismatch Repair: Other enzymes scan DNA post-replication to fix mismatches.

• DNA Damage: Caused by chemicals, radiation, or spontaneous changes.

• Nuclease: Cuts out damaged DNA; excision repair replaces it with correct bases.

• Nucleotide Excision Repair: Removes and replaces damaged DNA, e.g., UV-induced damage in skin cells.

Replicating the Ends of DNA Molecules

Linear chromosomes pose a challenge for replication at their ends. Specialized structures and enzymes address this issue.

• Telomeres: Repetitive nucleotide sequences at chromosome ends (e.g., TTAAGGG repeated 100–1,000 times).

• Function: Protect genes from shortening; act as buffer zones.

• Telomerase: Enzyme that extends telomeres in germ cells; not active in most somatic cells but active in some cancer cells, contributing to their immortality.

• Aging: Telomere shortening is linked to cellular aging.

Key Terms and Definitions

• DNA (Deoxyribonucleic Acid): The molecule that carries genetic information.

• Nucleotide: Building block of DNA, consisting of a nitrogenous base, sugar, and phosphate.

• Helicase: Enzyme that unwinds DNA.

• DNA Polymerase: Enzyme that synthesizes new DNA strands.

• Okazaki Fragment: Short DNA segment synthesized on the lagging strand.

• Telomere: Protective DNA sequence at chromosome ends.

• Telomerase: Enzyme that extends telomeres.

Example: DNA Replication Process

1. Helicase unwinds the DNA double helix.

2. Single-strand binding proteins stabilize the separated strands.

3. Primase synthesizes an RNA primer.

4. DNA polymerase adds nucleotides to the 3’ end of the primer, synthesizing the new strand.

5. On the lagging strand, Okazaki fragments are formed and joined by DNA ligase.

6. Proofreading and repair mechanisms correct errors and damage.

DNA Replication: Comparison of Leading and Lagging Strands

Key Equations

• Phosphodiester Bond Formation:

• Chargaff’s Rule:

Additional info: Telomerase is a ribonucleoprotein enzyme that carries its own RNA template for extending telomeres. Its activity is a focus of research in aging and cancer biology.