In-Depth Notes on DNA, Protein, and the Central Dogma

Overview of Cell Biology: DNA, Protein & the Central Dogma

Lecturer: Dr. Henry de Malmanche
Email: h.demalmanche@uq.edu.au

Key Resources:
Campbell et al. Biology, 12th edn: Chapters 5, 16, & 17

Key Concepts in DNA and Gene Expression

DNA as Genetic Material:
DNA (deoxyribonucleic acid) is the essential molecule that carries genetic information across generations. It consists of sequences of nucleotides, which encode for proteins, the building blocks of life. The genetic code is read in triplets, known as codons, each coding for specific amino acids.

Protein Functions:
Proteins serve a diverse range of roles essential for cellular structure and function, including but not limited to:

• Structural proteins (e.g., keratin, collagen) that provide support and shape to cells and tissues.

• Enzymes (e.g., DNA polymerase III, lactase) that catalyze biochemical reactions, significantly increasing their rates.

• Transport proteins that facilitate the movement of molecules across cell membranes (e.g., hemoglobin).

• Signaling proteins (e.g., hormones) that mediate communication between cells.

Gene Expression and the Central Dogma

Definition: The central dogma articulates the framework for understanding the flow of genetic information from DNA to RNA and ultimately to proteins. This principle underlies the mechanisms of genetic expression and regulation.

Transcription: This process involves the synthesis of messenger RNA (mRNA) from a DNA template, executed by the enzyme RNA polymerase. Transcription begins at a specific site known as the promoter and includes stages: initiation, elongation, and termination.

Translation: The process of translating the mRNA sequence into a polypeptide chain occurs at ribosomes, where transfer RNA (tRNA) brings amino acids to the growing polypeptide according to the mRNA codon sequence.

Key Processes:

• mRNA functions as an intermediary in gene expression, carrying genetic information from DNA to ribosomes.

• Eukaryotic cells undergo extensive post-transcriptional modifications, including splicing (removal of introns), 5’ capping (addition of a modified guanine nucleotide), and polyadenylation (addition of a poly-A tail), which enhance mRNA stability and translation efficiency.

• Mutation Effects: Mutations in DNA, caused by various factors (mutagens, replication errors, etc.), can lead to changes in protein structure and function, potentially resulting in genetic disorders or cancer.

DNA Structure and Function

Basic Structure:
DNA is a long linear polymer made up of four nucleotides: adenine (A), thymine (T), cytosine (C), and guanine (G). The sequence of these nucleotides encodes genetic information vital for life processes. Each nucleotide consists of a deoxyribose sugar, a phosphate group, and a nitrogenous base.

Double Helix:
DNA exists as a double helix structure, deliberately organized into two antiparallel strands that run in opposite directions, with complementary base pairing (A-T and G-C) ensuring structural integrity and accurate genetic replication.

Hydrogen Bonds:

• Adenine (A) pairs with Thymine (T) or Uracil (U) in RNA via two hydrogen bonds.

• Guanine (G) pairs with Cytosine (C) via three hydrogen bonds, making this pairing more stable than A-T pairing.

DNA Replication

Semi-Conservative Mechanism:
During replication, each strand of the original DNA serves as a template to synthesize a new complementary strand, resulting in two identical DNA molecules, each containing one old and one new strand.

Directionality:
DNA synthesis uniformly occurs in the 5’ to 3’ direction. DNA polymerase can only add nucleotides to the free hydroxyl group at the 3’ end of the growing strand.

Leading and Lagging Strands:

• Leading Strand: Synthesized continuously towards the replication fork.

• Lagging Strand: Synthesized in short fragments, known as Okazaki fragments, away from the direction of the replication fork; fragments are subsequently joined together.

Key Enzymes in DNA Replication:

• DNA Polymerase: Enzyme that synthesizes new DNA strands by adding nucleotides complementary to the template strand.

• Primase: Synthesizes short RNA primers required for DNA polymerase to initiate synthesis.

• Helicase: Unwinds the double helix, separating the two DNA strands at the replication fork.

• Topoisomerase: Alleviates the torsional strain created ahead of the replication fork by cutting and rejoining DNA strands.

• Ligase: Seals the nicks between Okazaki fragments on the lagging strand, forming a continuous DNA strand.

Summary of DNA Replication Process

Initiation: Begins at specific sites known as origins of replication, where the DNA unwinds and forms a replication bubble.

Elongation: Nucleotides are added to the 3’ end of the growing strand by DNA polymerase, extending the new DNA strand.

Termination: Replication concludes when the fork reaches the end of the DNA molecule; RNA primers are replaced by DNA nucleotides, and gaps are sealed by ligase, completing the new DNA strands.

Important Terms

• Central Dogma: The flow of genetic information from DNA to RNA to protein, essential for understanding gene expression.

• Transcription: The process of synthesizing RNA from a DNA template, crucial for gene expression.

• Translation: The process of synthesizing proteins from mRNA, where ribosomes read the mRNA to assemble amino acids into polypeptides.

• Nucleic Acids: The polymers that make up DNA and RNA, vital for genetic information storage and transmission.

• Nucleotides: The monomer units that constitute nucleic acids, each comprising a sugar, phosphate group, and nitrogenous base.

• Complementary Base Pairing: The principle that determines the pairing of bases in nucleic acids, facilitating accurate replication and transcription through A-T (or U) and G-C pairing.