Molecular Genetics: DNA Structure, Replication, and Heredity

The Molecular Basis of Heredity

DNA as the Carrier Molecule of Genetic Information

DNA is the molecule that carries the genetic information determining the biological characteristics of living beings.

Requirements for Genetic Material

1. Stable: Must maintain its structure.
2. Capable of Replication: Must be able to replicate and produce accurate copies.
3. Transmissible: Must be transmitted from one generation to another.
4. Susceptible to Change: Must be able to undergo changes (mutations) to allow for genetic variety.

Historical Discoveries

• DNA was first discovered by Miescher.
• The study involving bacteria that cause pneumonia (two strains: R and S) showed that the S strain causes death, the R strain is non-offensive, and the R strain can mutate into the S strain.
• Avery deduced that the transforming factor was the DNA molecule.
• Hershey and Chase deduced that the reproducible genetic material is DNA, not protein.

Genetic Material in Prokaryotes and Eukaryotes

In all prokaryotes, DNA is used for the synthesis of proteins. In eukaryotes, almost half of the DNA is repetitive. The genetic material includes both coding regions and non-coding regions.

• Eukaryotic DNA: Contains coding regions (exons) and non-coding regions (introns/repetitive DNA).
• Prokaryotic DNA: Generally non-repetitive and primarily coding.

DNA Replication

Models of DNA Replication

There are three proposed ways DNA replication could occur:

1. Conservative: The original double helix is maintained, and an entirely new double helix is synthesized.
2. Semiconservative: Each new double helix consists of one original (template) strand and one newly synthesized strand.
3. Dispersive: Each new double helix contains interspersed pieces of original and newly synthesized DNA.

Mechanism of Replication

Replication occurs during the S phase of the cell cycle, taking place in the nucleus of eukaryotes. The process is bidirectional.

Initiation of Replication

1. The first enzyme involved is Helicase, which separates the two DNA strands by breaking the hydrogen bonds, forming a replication bubble.
2. Tensions caused by unwinding are eliminated by Topoisomerases.
3. The separated strands are kept stable by Single-Strand Binding (SSB) proteins.

Synthesis of New Strands

New strands are formed by the enzyme DNA Polymerase III. Its characteristics include:

• It requires a DNA template strand.
• It synthesizes in the 5' to 3' direction.
• It uses nucleotide triphosphates.
• It cannot initiate synthesis on its own; it requires an RNA primer (synthesized by the enzyme Primase).

Continuous and Discontinuous Synthesis

As the original double helix separates, synthesis is continuous on one strand, called the leading strand (or conductora). Synthesis on the other strand, called the lagging strand (or retarded strand), is slower and discontinuous, forming short DNA segments called Okazaki fragments. These fragments are later joined by Ligase enzymes.

Completion

The newly synthesized strands wrap together, forming two new double helices.

Replication Differences: Prokaryotes vs. Eukaryotes

1. Eukaryotic DNA is associated with histones.
2. Prokaryotes typically have a single origin of replication, whereas eukaryotes have many origins.

Error Correction and Genetic Variability

DNA repairs itself using nuclease enzymes. Despite these corrective mechanisms, faults sometimes occur, leading to genetic variability.