2021_L13 DNA structure, type & function

Structures, Types and Functions

  • Presenter: Dr. Ahmad Tarmidi Sailan

Objectives

  • Explain the function of DNA as genetic material and its location in the cell.

  • Describe the structure and type of DNA relating to its function.

  • Elaborate on the properties of DNA.

  • Explain how DNA is arranged to form chromosomes.

  • Discuss repetitive sequences in the human genome.

  • Department of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry UKM.

DNA Location

  • DNA can be found in:

    • Nucleus

    • Mitochondria

Central Dogma: DNA to Protein

  • Represented in a space-filling model with color codes:

    • Carbon (C) - Black

    • Hydrogen (H) - White

    • Oxygen (O) - Red

    • Phosphorus (P) - Yellow

    • Nitrogen (N) - Blue

Historical Contributors to DNA Structure

  • James Dewey Watson (1928)

  • Francis Harry Compton Crick (1916-2004)

  • Maurice Hugh Frederick Wilkins (1916-2004)

  • Nobel Prize for Physiology or Medicine (1962); discovery in 1953.

DNA Structure Characteristics

  • Complimentary Strands:

    • Antiparallel orientation.

    • Consists of deoxyribose, phosphate, and base pairs.

  • Base Pairing:

    • 5' to 3' directionality.

    • Bases include Adenine (A), Thymine (T), Guanine (G), Cytosine (C).

    • Hydrogen bonds forming between:

      • A and T (2 H bonds)

      • G and C (3 H bonds).

Denaturation vs Renaturation

  • Tm (Melting Temperature):

    • Temperature at which half of the helical structure in DNA is lost.

Properties of DNA

  • Determined from melting curve, indicating:

    • Base composition (higher Tm equals higher G-C content).

    • Impact of pH and salt in DNA structure stability.

  • Hybridization:

    • Single-stranded DNA can hybridize between similar or different DNAs with homologous sequences.

    • Basis of genetic engineering/recombinant DNA technology.

    • Techniques include:

      • Southern Blot (DNA-DNA)

      • Northern Blot (DNA-RNA).

Exonucleases vs Endonucleases

  • Exonucleases:

    • Cleave nucleotides from the end of the DNA chain.

  • Endonucleases:

    • Cleave within the chain, creating single-stranded nicks.

Structural Forms of DNA

  • Three Types:

    • A-DNA: Right-handed

    • B-DNA: Right-handed (most common)

    • Z-DNA: Left-handed.

Characteristics of B-DNA

  • Structure:

    • Double helix with:

      • 10 residues per 360° turn.

      • 0.34 nm rise per residue.

      • Primarily consists of chromosomal DNA.

Properties of Z-DNA

  • Structural differences from B-DNA:

    • View types (end-on and side).

    • Major and minor grooves facilitating molecular interactions.

Structural Properties of DNA

  • Comparison of forms (A, B, Z):

    • Helix Direction: Right (A,B), Left (Z)

    • Residues per Turn: 11 (A), 10 (B), 12 (Z)

    • Rise in Helix: 0.255 nm (A), 0.34 nm (B), 0.37 nm (Z)

    • Pitch of Helix: 2.8 nm (A), 3.4 nm (B), 4.5 nm (Z).

Features of B- and Z-DNA

  • Major groove - wide; minor groove - narrow.

  • Grooves allow:

    • Binding of regulatory proteins (RBP).

    • Interaction with drugs like Actinomycin D (anticancer).

Circular DNA

  • Eukaryotes:

    • Long linear dsDNA in mitochondria and chloroplasts (closed circular).

  • Prokaryotes:

    • Supercoiled circular chromosomes, associated with histone-like proteins; plasmids are also circular.

Human Genome Organization (HUGO)

  • Aimed at mapping all genes.

    • One chromosome corresponds to one DNA double helix.

    • Contains:

      • Telomeres at ends.

      • Approximately 3 billion base pairs/nucleotides.

      • 30,000 genes distributed across 24 chromosomes.

      • 5% code for proteins.

Types of Repetitive DNA

  • Tandemly Repetitive DNA (Satellite DNA):

    • 10-15% of mammalian DNA; lengths from 1 to 10 bp.

    • Located at centromeres and telomeres; organized chromatin and prevent fraying.

  • Interspersed Repetitive DNA:

    • 25-40% of mammalian DNA; lengths from 100 bp to 10,000 bp.

    • Number of repetitions varies significantly.

Uses of Repetitive DNA

  • Understanding mutations and polymorphisms.

    • Single Nucleotide Polymorphisms (SNPs):

      • Useful in identifying disease susceptibility patterns.

  • Most human DNA (60-70%) consists of single or low copy number sequences.

Genetic Variation and Disease Susceptibility

  • Sequence variation occurs across 200-500 bp affecting humans.

    • Common variants account for 1% of the population (polymorphisms).

    • Rare alleles account for <1% of the population.

Relationship Between Structure and Function of DNA

  • DNA structure is crucial for:

    • Heredity and replication through complementary base pairing (A with T, G with C).

    • Repair mechanisms utilizing intact strands as templates.

    • Control of genetic expression ensuring transcription accuracy and regulation.

Conclusion

  • Presentation ended with a thank you.