Chapter 16

Morgan and his group discovered that genes are located on chromosomes, which consist of both DNA and proteins.
The specific genetic material responsible for heredity was unidentified until later experiments, particularly after 1940, established DNA as the genetic material.

Frederick Griffith's Experiment (1928)
  - Objective: Discover a vaccine for pneumonia.
  - Studied two strains of bacterium: pathogenic (harmful) and non-pathogenic (harmless).
  - Mixed heat-killed pathogenic strain with live harmless strain. Results:
    - Some live harmless cells became pathogenic, resulting in the death of the mouse.
  - This phenomenon is attributed to transformation, where harmless bacteria incorporated DNA from dead pathogenic cells, leading to changes in genotype and phenotype.
Hershey-Chase Experiment (1952)
  - Scientists Alfred Hershey and Martha Chase confirmed that DNA, not protein, is the genetic material using bacteriophages.
  - Bacteriophages: Consist of DNA or RNA within a protective protein coat.
  - Process: Injection of viral DNA into bacterial cells leads to reprogramming of the host’s cellular machinery to replicate viral components, resulting in the production of numerous new viruses until the bacterial cell bursts (lysis) and releases them.

Double Helical Structure of DNA (1953)
- Proposed by James Watson and Francis Crick.
- Structure: Two antiparallel strands with sugar-phosphate backbones and paired nitrogenous bases on the inside.

Technique: X-ray crystallography allowed the study of molecular structures.
Findings:
  - DNA is helical, with two strands forming a double helix.
  - The sugar-phosphate backbones are antiparallel, aligned in opposing directions relative to each other.
  - Uniform width of DNA was consistent with X-ray data showing purine and pyrimidine nitrogenous bases.

DNA (Deoxyribonucleic acid) is a polymer of nucleotides:
  - Each nucleotide consists of:
    - One sugar molecule (deoxyribose)
    - One phosphate group
    - One nitrogen base:
      - Adenine (A)
      - Thymine (T)
      - Guanine (G)
      - Cytosine (C)
Key Pairing Rule: - Equal amounts of A and T bases, and equal amounts of G and C bases.
- Nitrogenous bases: Purines (A, G) are double-ring structures; Pyrimidines (C, T) are single-ring structures.
RNA (Ribonucleic acid) serves as genetic material in some organisms (e.g., viruses), contains ribose sugar, and uracil (U) replaces thymine (T).

Importance: Resemblance of offspring to parents is due to accurate copying of genetic information.
Template Mechanism:
- Specific base pairing (A pairs with T, G pairs with C) allows each DNA strand to serve as a template for forming complementary strands.

Process: Occurs before meiosis and ensures faithful DNA passage to daughter cells during mitosis.

Semiconservative Model: Each daughter molecule includes one old strand from the parent molecule and one new strand.
Conservative Model: Two original strands rejoin; the old strands remain intact while new strands are formed.
Dispersive Model: Each strand is a mix of old and new fragments.

Speed and Accuracy: DNA replication is rapid and precise, initiates at origins of replication where strands separate, forming replication bubbles.
- Eukaryotes may have hundreds to thousands of origins.
Replication Fork: Y-shaped structure formed at replication bubbles, where double helix unwinds.
Vital Enzymes and Proteins:
  - Helicase: Untwists the double helix and separates strands by breaking hydrogen bonds at replication forks.
  - Single-strand binding proteins (SSBPs): Bind and stabilize single-stranded DNA.
  - Topoisomerase: Relieves tension ahead of the replication fork, preventing supercoiling by breaking, untwisting, and rejoining DNA strands.
  - Primase: Synthesizes an RNA primer (5-10 nucleotides) for initiating DNA synthesis.

DNA polymerases require primers and a template strand for action.
Nucleotide Addition: Each added nucleotide is a nucleoside triphosphate; energy is used when they lose two phosphates during synthesis.
Directionality of DNA Elongation:
- Leading strand synthesized continuously towards the replication fork.
- Lagging strand synthesized away from the fork in short Okazaki fragments, later joined by DNA ligase.
Antiparallel Synthesis: All new DNA is synthesized in the 5′ → 3′ direction.

DNA Polymerase: Checks for errors by proofreading as nucleotides are added, replacing incorrect ones.
Mismatch Repair: Further enzymes replace incorrectly paired nucleotides, akin to editing written text.
DNA Damage: Can arise from external agents (e.g. cigarette smoke, X-rays) or spontaneous changes.

A repair mechanism fixing DNA sections potentially damaged by UV light.
- Nuclease: Recognizes damage and excises the affected DNA segment.
- After removal, DNA polymerase fills the gap with new nucleotides using the complementary strand as a template and DNA ligase seals the remaining nick.

DNA mutation can lead to permanent nucleotide sequence changes, contributing to genetic variation and the emergence of new species.

Limitation in DNA Replication: DNA polymerases can only extend nucleotides at the 3′ end.
- Telomeres: Repetitive DNA sequences at chromosome ends act as protective caps that shorten with replication, limiting cell division and protecting against oncogenesis.

Role of Telomeres: Prevent the loss of essential genetic information during replication.
Telomerase: Extends telomeres, facilitating prolonged cell division, related to both tumor formation and cellular aging.

Chromosomal Composition: Consist of DNA tightly packed with proteins.
Bacterial Chromosomes: Supercoiled circular DNA found in nucleoid regions.
Eukaryotic Chromosomes: Linear DNA associated with histone proteins within the nucleus, packaged as chromatin.
Nucleosomes: Fundamental chromatin units comprising DNA wrapped around a core of histone proteins. Each nucleosome resembles a bead on a string.

Interphase Chromatin Structure: Mostly loosely packed (euchromatin); regions like centromeres and telomeres may condense into heterochromatin.
Histone Modifications: Chemical changes can alter chromatin condensation and influence gene expression.

The structural assertion of DNA and its replication mechanisms fundamentally determine the flow of genetic information through generations and highlight the intricate regulation surrounding DNA replication and repair, which play critical roles in inheritance and evolution.