The Molecular Basis of Inheritance Notes

Chapter 16: The Molecular Basis of Inheritance

Interphase Phases

  • Interphase consists of the following phases:

    • G1: Initial growth phase where the cell prepares for DNA synthesis.

    • S (Synthesis): DNA replication occurs; each chromosome consists of two identical sister chromatids after DNA synthesis.

    • G2: Second growth phase, preparing for mitosis.

  • Mitosis is considered the M phase where division occurs.

DNA Replication

  • Before replication, each chromosome contains a single DNA molecule.

  • After replication, each chromosome consists of 2 identical DNA molecules (sister chromatids) held together by cohesin proteins.

Evidence for DNA as Genetic Material

  • Frederick Griffith’s Experiment (1928):

    • Found that living R cells combined with heat-killed S cells caused mice to develop pneumonia.

    • Conclusion: some factor from dead S cells transformed R cells to pathogenic.

  • Oswald Avery (1944):

    • Demonstrated that DNA is the transforming factor that converts R cells to S cells.

  • Erwin Chargaff (1950):

    • Discovered

    • Equal amounts of A and T.

    • Equal amounts of G and C in DNA.

  • Alfred Hershey and Martha Chase (1952):

    • Experiments with bacteriophages confirmed that DNA (not protein) is the genetic material.

DNA Replication Models

  • Conservative Model: Entire parent double helix remains intact.

  • Semi-Conservative Model: Each daughter DNA molecule consists of one old strand and one new strand.

  • Dispersive Model: Parental DNA is dispersed into two new molecules.

  • Notably supported by experiments from Meselson and Stahl.

DNA Replication Process

  • DNA replication requires:

    1. Parental DNA molecule to serve as a template.

    2. Enzymes to perform the copying (e.g., DNA Polymerase).

    3. Building blocks (nucleotides) to create new copies.

  • Origins of Replication: DNA is separated to create replication bubbles.

    • Prokaryotic cells have a single origin, while eukaryotic cells can have hundreds or thousands.

  • Replication Fork: Y-shaped region where new DNA strands elongate.

Key Enzymes in DNA Replication

  • Helicases: Unwind the double helix at replication forks.

  • Single-Strand Binding Proteins: Stabilize single-stranded DNA.

  • Topoisomerases: Prevent overwinding of DNA by breaking and rejoining strands.

  • Primase: Synthesizes an RNA primer to initiate DNA strand synthesis.

  • DNA Polymerase III: Adds nucleotides to the growing DNA strand and synthesizes DNA in a 5' to 3' direction. Requires RNA primer to start.

  • DNA Polymerase I: Replaces RNA primers with DNA.

  • DNA Ligase: Joins Okazaki fragments on the lagging strand.

Leading vs. Lagging Strand Synthesis

  • Leading Strand: Synthesized continuously in the direction of the replication fork with a single RNA primer.

  • Lagging Strand: Synthesized discontinuously in segments (Okazaki fragments) which require multiple RNA primers. The synthesis occurs away from the replication fork.

Telomeres and Telomerase

  • Telomeres: Repeated DNA sequences at the ends of chromosomes that protect them during replication. Important for maintaining chromosome integrity.

  • During replication, lagging strands face issues at the ends resulting in gradual shortening of chromosomes.

  • Telomerase: Enzyme that extends telomeres, using an RNA template, thus prevents chromosome shortening. It is often activated in cancer cells to promote unlimited cellular division.