Nucleic Acids: Structures of DNA and RNA

Structures of DNA and RNA

  • Presented by Darren Gowers from the University of Portsmouth.

  • Presentation referenced: Lehninger Principles of Biochemistry, Sixth Edition, 2013, W. H. Freeman and Company.

Types of DNA Forms

  • A form: Right-handed helix, diameter approximately 26 Å, base pairs per helical turn: 11, helix rise per base pair: 2.6 Å, base tilt normal to helix axis: 20°, sugar pucker: C-3' endo, glycosyl bond: Anti conformation for pyrimidines.

  • B form: Right-handed helix, diameter approximately 20 Å, base pairs per helical turn: 10.5, helix rise per base pair: 3.4 Å, base tilt normal to helix axis: 6°, sugar pucker: C-2' endo, glycosyl bond: Anti conformation.

  • Z form: Left-handed helix, diameter approximately 18 Å, base pairs per helical turn: 12, helix rise per base pair: 3.7 Å, base tilt normal to helix axis: 7°, sugar pucker: C-2' endo for purines, glycosyl bond: Anti for pyrimidines, syn for purines.

Unusual DNA Structures

  • Triple Helical DNA (Triplexes): DNA structures that can incorporate a third strand, primarily found in certain regulatory regions and are associated with gene expression control.

  • Quadruplexes (Tetraplexes): Composed of guanine-rich sequences that form four-stranded structures, significant in telomere shortening and gene regulation.

Secondary Structures of DNA and RNA

  • DNA sequences can exhibit palindromes or repeats, crucial for structural stability and interactions:

    • Palindromes: sequences that read the same backward as forward (e.g., "TTAGCACGTGCTAA", its complement is "AATCGTGCACGATT").

    • Mirror repeats: two sequences that are complementary but reversed (e.g., "TTAGCACCACGATT" and its complement).

Hairpin and Cruciform Structures

  • Hairpins and Cruciforms: Formed by complementary sequences that can fold back on themselves, leading to unique secondary structures.

    • Example Sequence: TGCGATACTCATCG (folds to create hairpins).

  • Internal Loop and Bulge Structures: Occur when bases do not pair fully, resulting in unpaired regions, significant in RNA structure and function.

RNA Molecular Complexity

  • RNA molecules, like tRNA, fold into intricate structures due to base pairing and stacking interactions:

    • Enzyme RNase P from E. coli: Example of RNA with catalytic capabilities, structure demonstrated with complex base-pairing motifs.

    • 3D RNA Structure: Includes components like Guanine, Cytosine, and might have modifications like methylation on bases (e.g., 7-Methylguanine).

DNA and RNA Denaturation

  • Denaturation involves:

    • Covalent bonds remain intact, preserving the genetic code.

    • Breaking of hydrogen bonds between strands leading to strand separation.

    • Loss of base stacking, which causes increased UV absorbance.

    • Induction Factors: High temperatures or changes in pH can lead to strand denaturation, a reversible process termed annealing.

Temperature Effects on Denaturation

  • Denaturation Rates:

    • AT-rich DNA regions melt at lower temperatures compared to GC-rich regions due to their weaker hydrogen bonding.

  • Graphical Representation of Denaturation: Plotting percentage denaturation against temperature shows a characteristic curve with differing melting temperatures (T_m).

Radiation Effects on Nucleic Acids

  • UV Light: Induces pyrimidine clumping (e.g., thymine dimers formed, potential skin cancer mechanism).

  • Ionizing Radiation: X-rays and gamma rays can cause ring-opening and strand breaking, creating significant genomic damage that is frequently hard to repair.

  • Mutation Accumulation: Linked to aging and cancer; the repairing ability of cells varies by damage type, and some mutations can be hereditary.

Chapter 8 Summary

  • Revisits:

    • Functions of nucleotides and nucleic acids.

    • Names and structures of common nucleotides.

    • Structural bases for DNA function.

    • Reversible denaturation phenomena in nucleic acids.

    • Chemical foundations for mutagenesis.