Makindo Medical Notes

Related Subjects: |DNA and RNA short notes |DNA replication |DNA structure in Nucleus |Mitosis and Meiosis |Cell Cycle

🧬 DNA replication is the biological process by which a cell makes an identical copy of its DNA. This ensures that each daughter cell receives the same genetic material. It is a highly regulated, enzyme-driven process with extraordinary accuracy ✅.

📖 Key Concepts of DNA Replication

• Semi-Conservative Replication 🔄: Each new DNA molecule has one parental strand + one new strand.
• Replication Origin 🎯: Starting points where DNA unwinds.
  • Prokaryotes: 1 origin per chromosome.
  • Eukaryotes: multiple origins per chromosome (speeds up replication).
• Replication Fork 🍴: Y-shaped structure where DNA is unwound and new strands built.

🪜 Steps of DNA Replication

• Initiation 🚦:
  • Origin proteins bind and recruit Helicase 🌀 to unwind DNA.
  • SSBs (single-strand binding proteins) prevent re-annealing.
  • Primase lays down short RNA primers ✍️.
• Elongation ➡️:
  • DNA Polymerase adds nucleotides 5' → 3'.
  • Leading strand continuous 🟢; Lagging strand made in short Okazaki fragments 🟠.
  • DNA Polymerase I (prokaryotes) removes RNA primers and replaces with DNA.
  • DNA Ligase 🔗 seals Okazaki fragments.
  • Topoisomerase relieves supercoiling tension ahead of fork.
• Termination 🛑:
  • Replication ends when forks meet (prokaryotes) or at chromosome ends (eukaryotes).
  • Telomerase extends ends of eukaryotic DNA, preventing loss of genetic material.

🔧 Enzymes & Proteins in DNA Replication

• Helicase 🌀: Unwinds DNA.
• SSBs 🛡️: Stabilise unwound strands.
• Primase ✍️: Lays RNA primers.
• DNA Polymerases ⚙️: Add nucleotides; proofread errors.
• DNA Ligase 🔗: Seals nicks.
• Topoisomerase ✂️: Relieves torsional strain.
• Telomerase ⏳: Adds repeat sequences at chromosome ends.

🔎 Fidelity & Proofreading

• DNA replication has an error rate of 1 in 10⁹–10¹⁰ bases 📊.
• DNA polymerases have 3'→5' exonuclease activity (proofreading) ✅.
• This proofreading maintains genetic stability and prevents mutations.

⚠️ Clinical Relevance

• Cancer 🎗️: Replication errors → mutations in oncogenes/tumour suppressors.
• Genetic Disorders 🧩: Mutations in replication machinery cause Bloom syndrome, Werner syndrome.
• Infections 🦠: Antibiotics (e.g. fluoroquinolones, rifampin) target bacterial DNA replication.
• Chemotherapy 💊: Agents like methotrexate, cytarabine inhibit DNA synthesis in cancer cells.

📝 Summary

DNA replication ensures accurate transmission of genetic information 📚. It is semi-conservative, uses many specialised enzymes, and has proofreading for high fidelity. Understanding it is key to genetics, microbiology, oncology, and pharmacology 🔬.

📷 DNA Structure

📷 DNA Replication