Molecular Biology Essentials: DNA Structure, Replication, and Protein Synthesis
1. DNA Structure
Double Helix: Twisted-ladder shape.
Nucleotide: Sugar (deoxyribose) + Phosphate + Nitrogenous base.
Bases: Purines (Adenine [A], Guanine [G]); Pyrimidines (Cytosine [C], Thymine [T]).
Pairing: A pairs with T (2 Hydrogen bonds), C pairs with G (3 Hydrogen bonds).
Chargaff’s Rule: A = T, and C = G.
Antiparallel Strands: Run in opposite directions (5’→3′ and 3’→5′).
Key Scientists
Griffith: Discovered the transforming factor.
Avery: Identified DNA as the transforming factor.
Chargaff: Established base pairing rules.
Hershey & Chase: Proved DNA is the genetic material.
Franklin & Wilkins: Produced X-ray diffraction images of DNA.
Watson & Crick: Developed the double helix model.
2. DNA Replication (Semiconservative)
Enzymes Involved
Helicase: Unzips the DNA double helix.
Topoisomerase: Relieves supercoiling ahead of the fork.
Primase: Adds the initial RNA primer.
DNA Polymerase III: Adds new nucleotides in the 5’→3′ direction.
DNA Polymerase I: Replaces the RNA primer with DNA nucleotides.
Ligase: Joins Okazaki fragments on the lagging strand.
Telomerase: Extends the ends (telomeres) of linear chromosomes.
Replication Steps
Initiation: Helicase unwinds DNA, creating a replication fork.
Primer Binding: Primase adds an RNA primer to start synthesis.
Elongation: DNA Polymerase III adds nucleotides:
Leading Strand: Synthesis is continuous.
Lagging Strand: Synthesis is discontinuous, forming Okazaki fragments.
Joining: Ligase seals the gaps between fragments.
Termination: Replication concludes, often at telomeres.
3. RNA Structure & Types
Sugar: Ribose.
Bases: Adenine (A), Guanine (G), Cytosine (C), Uracil (U) replaces Thymine (T).
Structure: Typically single-stranded.
Types:
mRNA (messenger RNA): Carries the genetic code from DNA.
tRNA (transfer RNA): Brings specific amino acids; contains an anticodon.
rRNA (ribosomal RNA): Structural and catalytic component of ribosomes.
4. Protein Synthesis
Transcription (In the Nucleus): DNA → mRNA
RNA polymerase binds to the promoter region.
Elongation: RNA polymerase adds complementary RNA nucleotides.
Termination: Synthesis stops at a specific terminator sequence.
Translation (At the Ribosome): mRNA → Protein
An mRNA codon pairs specifically with a tRNA anticodon.
Ribosome Sites:
A site: Where the new tRNA carrying an amino acid enters.
P site: Holds the growing polypeptide chain.
E site: Where the empty tRNA exits.
Start Codon: AUG (codes for Methionine).
Stop Codons: UAA, UAG, UGA (signal termination).
Genetic Code Properties
Codon: A sequence of 3 nucleotides that specifies one amino acid.
The code is universal (used by most life) and redundant (multiple codons can code for the same amino acid).
5. Mutations
Gene Mutations (Point Mutations)
Point Mutation: A change in a single base pair.
Silent: No resulting amino acid change.
Missense: Results in a different amino acid.
Nonsense: Creates a premature stop codon.
Frameshift Mutation: Caused by insertion or deletion of bases, shifting the entire reading frame.
Chromosomal Mutations
Deletion: A segment of the chromosome is removed.
Duplication: A segment is repeated.
Inversion: A segment is reversed end-to-end.
Translocation: A segment moves to a non-homologous chromosome.
Nondisjunction: Failure of chromosomes to separate during meiosis, leading to abnormal chromosome numbers (e.g., aneuploidy).
Examples of Disorders
Down Syndrome: Trisomy 21 (three copies of chromosome 21).
Turner Syndrome: Monosomy X (XO).
Klinefelter Syndrome: XXY genotype.
Cri du Chat: Deletion on chromosome 5.
Progeria: Caused by a mutation in the LMNA gene.
Other Conditions: Chronic Myelogenous Leukemia (CML), Hemophilia A, and Charcot-Marie-Tooth disease result from various specific mutations.
6. Causes & Effects of Mutations
Causes (Mutagens)
Exposure to radiation (e.g., X-rays, gamma rays).
Exposure to certain chemicals.
Infection by certain viruses.
Effects
Harmful: Can lead to genetic diseases or disorders.
Beneficial: Can lead to adaptation, increased diversity, and evolution.
7. Key Techniques
Karyotyping: Technique used to visualize and analyze chromosomes to detect large-scale abnormalities.
Central Dogma Summary: DNA → RNA → Protein.
Replication Principle: Semiconservative replication ensures each new DNA molecule contains one old strand and one newly synthesized strand.
Mutation Impact: Mutations can be silent, harmful, or beneficial, affecting either individual genes or entire chromosomes.
