DNA is the blueprint of life, storing genetic information in its double helix structure. Its unique composition of sugar-phosphate backbones and complementary base pairs allows for accurate replication and transcription, ensuring the faithful transmission of hereditary traits.

DNA's structure isn't static - it can adopt different conformations and levels of supercoiling. These variations play crucial roles in gene regulation and cellular processes. Enzymes like topoisomerases help manage DNA's topology, making them important targets for medical treatments.

DNA Structure and Key Components

Structure of DNA double helix

• Composed of two antiparallel polynucleotide strands wind around each other to form right-handed double helix
  • Each polynucleotide strand consists of sugar-phosphate backbone with nitrogenous bases attached
    • Deoxyribose, a pentose sugar
    • Phosphate groups connect 3' carbon of one sugar to 5' carbon of next sugar
    • Nitrogenous bases: adenine (A), thymine (T), guanine (G), and cytosine (C)
  • Two strands held together by hydrogen bonds between complementary base pairs
    • A pairs with T via two hydrogen bonds
    • G pairs with C via three hydrogen bonds
  • Double helix has major groove and minor groove, important for protein-DNA interactions (transcription factors)

Antiparallel structure and base pairing

• Antiparallel structure
  • Two polynucleotide strands run in opposite directions (5' to 3' and 3' to 5')
  • Allows formation of stable double helix
  • Facilitates semiconservative replication of DNA (each strand serves as template)
• Complementary base pairing
  • Ensures specificity and accuracy of DNA replication and transcription
  • Allows storage and transmission of genetic information (heredity)
  • Enables repair of damaged DNA through use of complementary strand as template (DNA repair mechanisms)

DNA Conformations and Topology

Conformations of DNA

• B-DNA
  • Most common conformation under physiological conditions
  • Right-handed double helix with 10.5 base pairs per turn
  • Wide major groove and narrow minor groove
• A-DNA
  • Formed under dehydrating conditions or in presence of certain ions (ethanol, trifluoroethanol)
  • Right-handed double helix with 11 base pairs per turn
  • Deep and narrow major groove, wide and shallow minor groove
• Z-DNA
  • Left-handed double helix with 12 base pairs per turn
  • Formed in regions with alternating purine-pyrimidine sequences, especially alternating G-C base pairs (CpG islands)
  • Narrower and more elongated than B-DNA
  • May play role in gene regulation and DNA-protein interactions (transcriptional control)

DNA supercoiling and topoisomerases

• DNA supercoiling
  • Twisting or coiling of DNA double helix around its own axis
  • Can be positive (overwound) or negative (underwound)
  • Affects DNA replication, transcription, and other cellular processes (chromatin structure)
  • Supercoiling influenced by linking number ($Lk$), sum of twist ($Tw$) and writhe ($Wr$)
    • $Lk = Tw + Wr$
    • Twist refers to number of helical turns in DNA
    • Writhe refers to number of times DNA axis crosses itself
• Topoisomerases
  • Enzymes regulate DNA supercoiling by introducing temporary single-strand (type I) or double-strand (type II) breaks in DNA
  • Allow DNA to unwind or relax, facilitating processes such as replication and transcription
  • Examples: topoisomerase I (type I) and topoisomerase II (type II)
  • Inhibition of topoisomerases can lead to DNA damage and cell death, making them targets for anticancer and antibacterial drugs (etoposide, ciprofloxacin)