DNA Structure and Function

Components of DNA

DNA (deoxyribonucleic acid) is the hereditary material in all living organisms. Its structure and composition are fundamental to understanding genetics and molecular biology.

• Nucleotides: The building blocks of DNA, each consisting of:

  • 5-carbon sugar (deoxyribose)

  • Phosphate group

  • Nitrogenous base

• Nitrogenous Bases: Four types:

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

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

• Chargaff’s Rules: In any DNA molecule, the amount of adenine equals thymine, and the amount of guanine equals cytosine.

DNA Double Helix

• DNA is a double-stranded molecule, with strands held together by hydrogen bonds between bases.

• The sugar-phosphate backbone forms the structural framework, running antiparallel (opposite directions).

• Base pairing rules: A pairs with T, G pairs with C.

• The sequence of base pairs encodes genetic information.

• The molecular shape is a double helix, resembling a spiral staircase, discovered by Watson, Crick, and Franklin.

DNA Replication

Overview of DNA Replication

DNA replication is the process by which DNA copies itself before cell division, ensuring genetic continuity.

• Replication is semiconservative: each new DNA molecule contains one old and one new strand.

• Replication begins at multiple origins of replication (specific nucleotide sequences).

• Helicase enzymes unwind and "unzip" the DNA strands by breaking hydrogen bonds.

• Single-strand binding proteins stabilize the open strands, forming replication forks.

• Primers (short RNA segments made by primase) initiate synthesis.

• DNA polymerase adds new nucleotides to the 3' (unbound OH) end, synthesizing in the 5' to 3' direction.

• Leading strand is synthesized continuously; lagging strand is synthesized discontinuously in Okazaki fragments (100-200 nucleotides in eukaryotes), joined by DNA ligase.

• Replication errors are proofread and repaired by various enzymes.

Replication Steps

1. Enzymes break bonds between DNA strands.

2. Strands unwind and expose bases.

3. Free nucleotides pair with exposed bases according to base pairing rules.

4. New DNA molecules wind into double helices.

Chromatin Structure

Organization of Chromosomes

In eukaryotic cells, DNA is packaged with proteins to form chromatin, allowing it to fit into the nucleus and regulate gene expression.

• Histones: Proteins responsible for the first level of DNA packing.

• Unfolded chromatin appears as "beads on a string," with each bead being a nucleosome (DNA wrapped twice around a core of eight histones).

• Histone tails protrude from nucleosomes and play a role in gene regulation.

Protein Synthesis

Overview

Protein synthesis is the process by which cells decode genetic information to build proteins, which are essential for cellular functions.

• Two main steps: Transcription and Translation.

• DNA → Transcription → mRNA → Translation → Protein

• Three types of RNA involved:

  • Messenger RNA (mRNA)

  • Ribosomal RNA (rRNA)

  • Transfer RNA (tRNA)

• RNA differs from DNA:

  • Sugar is ribose (not deoxyribose)

  • Uracil (U) replaces thymine (T)

  • Single-stranded, not double helix

Transcription

Transcription is the synthesis of RNA from a DNA template, occurring in the nucleus.

• Only a specific gene (transcription unit) is copied.

• RNA polymerase binds to the promoter region and separates DNA strands.

• RNA polymerase links RNA nucleotides complementary to the DNA template (5' to 3').

• Transcription stops at the terminator sequence; RNA detaches and DNA reforms its double helix.

• RNA is read in groups of three bases called codons, each coding for an amino acid.

• There are 64 possible codons but only about 20 amino acids, leading to redundancy.

RNA Modification

Before mRNA leaves the nucleus, it undergoes modifications to become mature mRNA.

• A 5' cap (modified guanine nucleotide with triphosphate group) is added to the 5' end.

• A poly-A tail (long sequence of adenine) is added to the 3' end.

• Introns (non-coding sequences) are removed; exons (coding sequences) are spliced together.

• These modifications protect mRNA from degradation and facilitate translation.

Translation

Translation is the process by which mRNA is decoded to synthesize polypeptides (proteins), occurring in the cytoplasm at ribosomes.

• tRNA brings amino acids to the ribosome.

• Each tRNA has:

  • An attachment site for an amino acid

  • An anticodon (nucleotide triplet) that pairs with the mRNA codon

• Ribosomes consist of two subunits (large and small), made of rRNA and proteins.

• Ribosomes have binding sites for mRNA and three tRNA sites:

  • P site: Holds tRNA with growing polypeptide chain

  • A site: Holds tRNA with next amino acid

  • E site: Exit site for discharged tRNA

Steps of Translation

1. Initiation: mRNA binds to small ribosomal subunit; initiator tRNA (methionine) binds start codon (AUG); ribosomal subunits assemble.

2. Elongation: tRNAs bring amino acids; peptide bonds form; tRNAs shift through ribosome sites; mRNA moves along.

3. Termination: Stop codon (UAA, UAG, UGA) is reached; polypeptide and mRNA are released; ribosomal subunits separate.

Mutations

Gene Mutations

Mutations are changes in the genetic code, which can affect protein synthesis and organismal traits.

• Gene mutation: Small-scale changes (one or a few bases).

• Types:

  • Base pair substitution: One base is replaced by another.

  • Silent mutation: No effect due to genetic code redundancy.

  • Missense mutation: Codes for a different amino acid (e.g., sickle cell anemia).

  • Nonsense mutation: Changes codon to a stop codon, often resulting in nonfunctional protein.

  • Frameshift mutation: Insertion or deletion shifts the reading frame, altering amino acid sequence.

• Mutations can occur spontaneously during DNA replication or be induced by mutagens (e.g., UV light).

• Mutagens causing cancer are called carcinogens.

• Mutations can be inherited and are a source of evolutionary change and diversity.

Mutation Rate

• Probability of mutation in a gene per generation: 1/10,000 to 1/100,000 in eukaryotes.

Summary Table: DNA vs. RNA

Key Equations and Concepts

• Base Pairing:

• Semiconservative Replication:

  • Each new DNA molecule:

• Central Dogma:

Example: Sickle Cell Anemia

A missense mutation in the gene coding for hemoglobin results in a single amino acid change, causing sickle cell anemia.

Additional info: The redundancy of the genetic code means some mutations do not affect the protein (silent mutations), while others can have significant effects (missense or nonsense mutations).