Structure of DNA

Introduction

• Nucleus: DNA is housed in the nucleus, requiring a basic understanding of its structure and functions.

Structure of the Nucleus

Nuclear Envelope

• Double Membrane: Composed of a phospholipid bilayer.
• Nuclear Pores: Proteins aiding transport between the nucleus and cytoplasm.

Nucleoplasm

• Components:
  • Nucleolus: Site of rRNA synthesis and ribosomal subunit assembly.
  • Chromatin: Composed of DNA and histone proteins.

Inner and Outer Membranes

• Outer Membrane: Studded with ribosomes.
• Inner Membrane: Contains lamins, involved in structural framework and interaction with chromatin.

Chromatin Details

• Histone Proteins: Assist in condensing DNA into compact structures.
• Types:
  • Heterochromatin: Highly condensed, no transcription.
  • Euchromatin: Loose, allows transcription.

Chromosome and DNA Structure

• Chromatin to Chromosome: During replication, chromatin condenses into chromosomes.
• Nucleosomes: DNA wrapped twice around histone octamers (H2A, H2B, H3, H4).
• Linker Histone (H1): Holds nucleosomes together.

DNA Structure

• Sugar-Phosphate Backbone: Formed by phosphodiester bonds.
• Nitrogenous Bases:
  • Purines: Adenine (A), Guanine (G).
  • Pyrimidines: Cytosine (C), Thymine (T).
  • Complementarity: A pairs with T, G pairs with C.

Epigenetic Control

• DNA Methylation: Addition of methyl groups to CpG islands inhibits transcription.
• Histone Modification:
  • Acetylation: Relaxes DNA-histone interaction, promotes transcription.
  • Methylation: Can either relax (single methyl group) or tighten (multiple methyl groups) DNA-histone interaction.

Clinical Relevance

• Drug-Induced Lupus: Autoimmune reaction targeting histone proteins.
• Huntington's Disease: Associated with increased deacetylation, inhibiting transcription.
• Drug Inhibition of Nucleotide Synthesis:
  • Purine Synthesis Inhibitors: 6-Mercaptopurine, Azathioprine.
  • Pyrimidine Synthesis Inhibitors: Methotrexate, Trimethoprim.
  • Dual Inhibitors: Hydroxyurea.

DNA Topology

• Double Helix: Anti-parallel strands with major and minor grooves.
• Grooves: Minor groove is a target for replication enzymes and certain drugs like dactinomycin inhibiting replication.

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This lecture covered a detailed overview of the DNA structure, its packaging in the nucleus, various clinical implications, and the importance of epigenetics in gene expression. Understanding these concepts is crucial for higher-level biology studies and medical examinations like USMLE.