quiz 1

Deoxyribose Nucleic Acid

7.1 DNA Is the Hereditary Molecule of Life

• Long before DNA was established as the hereditary molecule, the following five characteristics of hereditary material were identified:

  1. Localized to the nucleus and a component of chromosomes.

  2. Present in stable form in cells.

  3. Sufficiently complex to contain the information necessary for the structure, function, development, and reproduction of an organism.

  4. Able to accurately replicate itself, ensuring that daughter cells contain the same information as the parent cells.

  5. Mutable, undergoing a low rate of mutations that introduce genetic variation and serve as a foundation for evolutionary change.

Additional Features of Hereditary Material

• The identified characteristics underscore a comprehensive understanding of DNA's functions and importance in genetics.

The Transformation Factor Responsible for Heredity

• Frederick Griffith conducted experiments using two strains of Pneumococcus bacteria:

  • S strain (smooth) caused fatal pneumonia in mice.

  • R strain (rough) did not cause disease in mice.

  • These strains are categorized into four antigenic types (I, II, III, and IV) that cannot be altered into a different type by mutation alone.

  • A single gene mutation can change an S (smooth) strain into an R (rough) strain of the same antigenic type.

Griffith's Key Experiment

• During the experiment, the injection of live type SIII (smooth strain) led to the death of mice, whereas live type RII did not cause any deaths. The critical observations included:

  1. Injecting live type SIII into mice resulted in death.

  2. Injecting heat-killed type SIII resulted in mice surviving.

  3. Injecting living type RII led to healthy mice.

  4. Injecting heat-killed type SIII along with live type RII resulted in dead mice, indicating that RII was transformed into SIII.

• Conclusion: The hereditary molecule transformed RII bacteria into SIII bacteria, providing a foundation for understanding genetic transformation in bacteria.

Griffith's Proposal

• Griffith proposed that the transformation factor was the hereditary molecule that transformed RII into SIII, carrying hereditary information, although he could not identify the molecule responsible.

• He described transformation, the process by which bacteria can transfer DNA, indicating the necessity for additional tests to identify the transforming material.

DNA Is the Transformation Factor

• Avery, MacLeod, and McCarty built on Griffith's work by using heat-killed SIII bacteria combined with live RII bacteria:

  • The extract of heat-killed SIII bacteria was divided into aliquots treated to destroy either DNA, RNA, proteins, or lipids and polysaccharides.

• Observation: All aliquots killed the mice except the aliquot that had DNA destroyed.

Figure 7.2 - Avery, MacLeod, and McCarty's Experiment

• They concluded that:

  • Transformation is not disrupted by the removal of lipids, polysaccharides, proteins, or RNA.

  • Therefore, DNA is the hereditary molecule required for transformation.

7.2 The DNA Double Helix

• DNA was identified through the experiments of Rosalind Franklin, who presented its helical structure, which was modeled by James Watson and Francis Crick. The crucial aspects of its structure include:

  • Simplistic Composition: It's composed of two strands forming a double helix due to the interaction of nitrogenous bases.

  • Polynucleotide Chains:

  • DNA consists of two polynucleotide chains interconnected by covalent phosphodiester bonds.

  • Each polynucleotide chain contains four kinds of nucleotides, which contribute to the DNA's complexity.

  • Nitrogenous Bases:

  • Four bases: Adenine (A), Thymine (T), Guanine (G), and Cytosine (C)

  • Purines: Adenine (A) and Guanine (G) (double-ring structure).

  • Pyrimidines: Thymine (T) and Cytosine (C) (single-ring structure).

DNA Nucleotides

• A DNA nucleotide is composed of:

  • A sugar (deoxyribose),

  • One of the four nitrogenous bases,

  • Up to three phosphate groups (for dNTPs).

Assembly of Polynucleotide Chains

• Individual nucleotides assemble into chains via DNA polymerase (primarily DNA polymerase III), which catalyzes the formation of a phosphodiester bond between the 3' hydroxyl group of one nucleotide and the 5' phosphate group of another, leading to the creation of a DNA strand.

DNA Replication Mechanism

• DNA replication is characterized as semiconservative and bidirectional:

  • One original strand serves as a template for replication, with nucleotides being added exclusively to the 3' hydroxyl group.

  • The integration of new nucleotides occurs primarily during the S phase of the cell cycle.

• The process of DNA replication sees unwinding, forming a replication fork, where new daughter strands are synthesized.

Competing Models of Replication

• Following the elucidation of DNA’s structure, three models of replication emerged:

  1. Semiconservative replication (each strand serves as a template).

  2. Conservative replication (parental DNA remains intact and produces a new double helix).

  3. Dispersive replication (new and old DNA strands are mixed).

• Meselson and Stahl conducted experiments to confirm the semiconservative model, showing that after one replication cycle, the DNA molecules exhibited densities indicative of both parental and newly synthesized strands.

Origin and Directionality of Replication

• Bacterial DNA replication is often bidirectional with replication proceeding from a single origin.

• In contrast, eukaryotic chromosomes have multiple origins of replication due to their linear structure, allowing simultaneous replication at several sites.

Telomerase and Telomere Function

• Telomeres prevent chromosome degradation, aiding in maintaining the integrity of the genome during cell division.

• In most somatic human cells, telomeres shorten with division; however, they are maintained in germline cells through the action of the enzyme telomerase.

• The telomerase complex, which contains RNA complementary to telomere sequences, adds additional repeats to the chromosomes.

Telomere Implications

• Long telomeres are linked to cellular longevity and reproductive success while telomere shortening can trigger apoptosis and limit cellular lifespan (Hayflick limit).

• The activation of telomerase in somatic cells poses as a potential vector towards increasing life spans but also raises concerns given that most cancer cells exhibit telomerase activity.