Understanding the Structure of DNA

Sep 12, 2024

Structure of DNA Lecture Notes

Introduction

  • Discussion about the structure of DNA and its relation to the nucleus.
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The Nucleus

Components of the Nucleus

  • Nuclear Envelope: Double membrane structure (phospholipid bilayer).
  • Nuclear Pores: Protein structures that facilitate transport in and out of the nucleus.
  • Nucleoplasm: The substance within the nucleus, containing various components.

Key Components of the Nuclear Envelope

  • Outer Membrane: Ribosome-studded, involved in mRNA translation to the rough endoplasmic reticulum.
  • Inner Membrane: Contains lamins, which provide structural support and interact with chromatin.
    • Pathology: Mutation in lamin A leads to Progeria (accelerated aging).

Nuclear Pores

  • Function: Allow transport of mRNA out and nucleotides in.
  • Example: mRNA exits and nucleotides enter for DNA synthesis.

Nucleoplasm Components

  • Nucleolus: Site of rRNA synthesis and ribosomal subunit formation.
  • Chromatin: DNA and histone proteins that condense DNA into a compact structure.
    • Histones: Positively charged proteins that interact with negatively charged DNA.
    • Types of Chromatin:
      • Heterochromatin: Highly condensed, transcriptionally inactive.
      • Euchromatin: Loosely packed, transcriptionally active.

DNA Structure

Chromatin to Chromosomes

  • Chromatin condenses into chromosomes during cell replication.
  • Understanding hierarchical structure of DNA:
    • Loopy continuous fibers.
    • Tight helical fibers.
    • Wrapped around histone proteins forming nucleosomes.

Nucleosomes

  • Composition: Octamer of histone proteins (H2A, H2B, H3, H4) with DNA wrapped around it.
  • Epigenetic Modifications: Influence gene expression.

DNA Nucleotide Structure

Constituents of Nucleotides

  • Nitrogenous Bases:
    • Purines: Adenine (A) and Guanine (G) - two rings.
    • Pyrimidines: Cytosine (C) and Thymine (T) - single ring (Uracil in RNA).
  • Pentose Sugar: Ribose (RNA) or Deoxyribose (DNA).
    • Deoxyribose lacks an -OH group on the second carbon.
  • Phosphate Group: Negative charge, binds to the fifth carbon of the sugar.

Nucleosides vs Nucleotides

  • Nucleoside: Pentose sugar + nitrogenous base.
  • Nucleotide: Nucleoside + phosphate group.

DNA Strand Formation

Complementarity

  • A pairs with T (2 hydrogen bonds).
  • G pairs with C (3 hydrogen bonds).
  • Importance of hydrogen bonds in stability.

Antiparallel Nature of DNA

  • One strand runs 5' to 3', the other 3' to 5'.
  • Phosphodiester bonds formed between 5' phosphate and 3' hydroxyl groups.

Three-Dimensional Structure of DNA

  • Forms a double helix with major and minor grooves.
  • Major Groove: Larger groove for enzyme binding.
  • Minor Groove: Smaller groove, significant for drug interactions (e.g., Dactinomycin).

Clinical Relevance

Drug-Induced Lupus

  • Antibodies produced against histone proteins.
  • Drugs causing lupus: Sulfonamides, Hydralazine, Isoniazid, Procainamide, Phenytoin.

Huntington's Disease

  • Increase in deacetylation decreases transcription of growth factors, leading to neuron injury.

Anti-Cancer Drugs

  • Drugs inhibiting nucleotide synthesis (e.g., 6-mercaptopurine, azathioprine, methotrexate) can prevent DNA replication in cancer cells.

Conclusion

  • Summary of DNA structure and its significance in genetics and medical relevance.