The Molecular Basis of Inheritance

Chapter 16: The Molecular Basis of Inheritance

Nucleus and DNA Storage

  • Nucleus: The membrane-bound organelle where genetic material (DNA) is stored in eukaryotic cells.
  • Nucleolus: A structure within the nucleus involved in ribosome production.
  • DNA Location:
    • In eukaryotes: DNA is stored in the nucleus.
    • In prokaryotes: DNA is found in a region called the nucleoid.

Key Figures in DNA Discovery

  • James Watson and Francis Crick: Developed the double helix model of DNA.
  • Rosalind Franklin: Used X-ray crystallography to analyze DNA structure. Established the importance of the antiparallel nature of DNA strands (the backbones run in opposite directions).

DNA Structure

  • Chromosome: DNA molecule that has coiled into a compact structure.
  • Supercoils: Extra twists in the DNA structure to fit within the confines of the cell.
  • Double Helix Model: Two strands of DNA wound around each other.
  • Components:
    • Histones: Proteins around which DNA is coiled.
    • Nucleotides: Basic units of DNA, consisting of a phosphate group, sugar (deoxyribose), and a nitrogenous base.
    • Nitrogenous Bases:
    • Cytosine (C)
    • Thymine (T)
    • Adenine (A)
    • Guanine (G)
  • Sugar-Phosphate Backbone: Alternating sugar and phosphate groups create the backbone of the DNA structure.
  • 5′ and 3′ Ends: DNA strands have distinct ends, which are crucial for replication and directionality.

Antiparallel Strands

  • One strand has the 5′ carbon of sugar in the upward position, while the complementary strand has the 3′ carbon in the upward position. This orientation is essential for DNA functions, including replication.

Base Pairing Rules

  • Initially, Watson and Crick hypothesized that bases paired similarly (A with A, C with C) but found this resulted in inconsistent widths.
  • Correct Base Pairing:
    • Pairing a purine with a pyrimidine (A with T and G with C) provided a uniform width in the double helix structure.
  • Hydrogen Bonds: Nitrogenous base pairs are held together by hydrogen bonds:
    • Adenine (A) to Thymine (T) - 2 hydrogen bonds.
    • Guanine (G) to Cytosine (C) - 3 hydrogen bonds.

Cell Cycle Overview

  • Cell Cycle: Sequence of events from the formation of a cell to its division into two daughter cells.
    • S Phase (Synthesis Phase): Cell growth and DNA replication occurs, preparing for cell division.

DNA Replication and Repair

Concept 16.2: Role of Proteins in DNA Replication and Repair
  • Accurate DNA replication is essential for offspring resemblance and the transmission of genetic material.
  • DNA Replication: Involves copying of DNA to ensure that each daughter cell receives identical genetic information.
Basic Principle of DNA Replication
  • Each DNA strand serves as a template, yielding two identical daughter molecules via semi-conservative replication: one new strand and one template strand in each new DNA molecule.
Mechanism of DNA Replication
  • Origins of Replication: Specific sites where DNA strands separate to form replication bubbles.
  • Key Enzymes Involved in DNA Replication:
    • DNA Polymerase: Adds nucleotides in a precise sequence (G-C and A-T) in the 5′ to 3′ direction. Requires a primer to initiate synthesis.
    • Primase: Synthesizes an RNA primer at the 5′ end of the leading strand and 5′ end of each Okazaki fragment of the lagging strand.
    • Helicase: Unwinds the parental double helix at the replication forks.
    • Single-Strand Binding Proteins: Stabilize single-stranded DNA until used as a template.
    • Topoisomerase: Relieves overwinding strain ahead of replication forks by breaking, swiveling, and rejoining DNA strands.
    • DNA Ligase: Joins Okazaki fragments on the lagging strand and links the new DNA to the adjacent strand.
Leading and Lagging Strands
  • Leading Strand: Synthesized continuously in the direction of the replication fork.
  • Lagging Strand: Synthesized in discontinuous chunks known as Okazaki fragments, which are later joined by DNA ligase.

Proofreading and Repair Mechanisms

  • DNA Polymerases: Proofread the newly synthesized DNA, correcting any incorrect nucleotides during replication.
  • Mismatch Repair: Enzymes replace incorrectly paired nucleotides that escape the proofreading process.
  • Damage Repair: DNA can be damaged by environmental factors (chemicals, X-rays) and spontaneous changes. In nucleotide excision repair, a nuclease excises damaged areas and replaces them with new nucleotides.
Efficiency of DNA Polymerases
  • Error Rate: DNA Polymerase III is highly accurate, with only 1 mistake per 10^7 deoxyribonucleotides added.
  • Consequences of Uncorrected Mistakes: If errors are not corrected, they can lead to mutations, defined as permanent changes in the DNA sequence.