DNA: The Genetic Material

Essentials of the Living World

Chapter 11: DNA: The Genetic Material

• Focus: Understanding DNA as the molecule that stores heredity.

Discovering the Structure of DNA

• Deoxyribonucleic Acid (DNA) Structure:
    - DNA is described as an anti-parallel, double-stranded helix.
    - Located in:
      - Nucleus (nuclear DNA)
      - Mitochondria (mitochondrial DNA)

• Nucleotides:
    - DNA comprises subunits called nucleotides, which consist of three components:
      - A central deoxyribose sugar
      - A phosphate group
      - An organic nitrogen-containing base
    - Nitrogenous Bases:
      - Purines (2 rings):
        - Adenine (A)
        - Guanine (G)
      - Pyrimidines (1 ring):
        - Cytosine (C)
        - Thymine (T)

Importance of Hydrogen Bonds in DNA

• The hydrogen bonds between nitrogenous bases hold the two strands of DNA together.
    - Example Pairings:
      - Adenine (A) pairs with Thymine (T)
      - Cytosine (C) pairs with Guanine (G)
• Key Distances in DNA Structure:
    - Length between base pairs: $0.34 ext{ nm}$
    - Full turn of helix: $3.4 ext{ nm}$

DNA Replication: S Phase of the Cell Cycle

• Extensive process involving numerous enzymes and proteins.
• Duration: Takes hours to copy all human DNA (more than 6 billion base pairs).
    - E. coli (bacteria) replication speed: approximately $500$ nucleotides per second.
    - Human cells replication speed: approximately $50$ nucleotides per second.

Origin of Replication

• Defined as short stretches of DNA with specific nucleotide sequences where replication initiates.
    - Eukaryotic chromosomes may have hundreds or thousands of origins of replication.
    - Proteins recognize the sequence, attach, and unwind the DNA, forming a replication "bubble".
    - Replication progresses bidirectionally from each origin.

Key Proteins & Nucleotides Involved in DNA Replication

1. DNA Polymerases:
      - Function: Replicates DNA in the $5' <br /> ightarrow 3'$ direction by catalyzing synthesis of new DNA.
2. DNA Helicase:
      - Function: Unwinds and separates parental DNA strands into template strands.
3. DNA Ligase:
      - Function: Joins or seals gaps, nicks, and spaces between DNA strands.

Detailed Mechanism of DNA Replication

• Leading and Lagging Strands:
    - Helicase unwinds the double helix for about $1,000$ nucleotides.
    - DNA polymerase builds complementary new strands, working in opposite directions on the leading and lagging strands.
    - DNA ligase connects newly formed segments on the lagging strand.

Proofreading and Repairing DNA

• 3’ → 5’ Exonuclease Activity (Proofreading Activity):
    - DNA polymerase checks each nucleotide against the template.
    - If mispaired, the nucleotide is removed and synthesis resumes.

• Mismatch Repair:
    - Corrections on mistakes overlooked by DNA polymerase.
    - Other enzymes remove and correct incorrectly paired nucleotides.

• Nucleotide Excision Repair:
    - Involves cutting a segment of damaged DNA using nuclease.
    - Gap filled by DNA polymerase and sealed by DNA ligase.

• Mutation:
    - Defined as a permanent alteration in the DNA sequence.

Telomeres

• Eukaryotic chromosomal DNA ends are marked by special nucleotide sequences called telomeres:
    - Telomere Sequence: $TTAGGG$ (repeated $100-1000$ times).
• Function of Telomeres:
    - They do not stop DNA shortening but do delay the erosion of genes near DNA ends.
    - Proposed connection: Telomere shortening linked to the aging process.
    - Telomere shortening in sex cells can lead to missing essential genes in gametes.
• Telomerase:
    - Enzyme lengthening telomeres in sex cells.
    - Shortening may prevent cancer by limiting cell division.
    - Evidence of telomerase activity in cancer cells suggests a mechanism for persistent growth.

Aging Process and Telomere Shortening

• Telomeres shorten over time leading to cessation of cell division and cellular aging.

Changes in Chromosome Structure

• Deletions:
    - Loss of a piece of chromosome (e.g., Williams Syndrome from loss on chromosome $7$ affecting the elastin gene).
• Duplications:
    - Presence of a segment more than once in the same chromosome.
• Inversions:
    - A segment of a chromosome is inverted 180 degrees.
• Translocations:
    - Movement of chromosome segments between non-homologous chromosomes.
    - Example:
      - Alagille Syndrome: Often due to translocation between chromosomes $2$ and $20$ leading to various physical abnormalities.
      - Chronic Myelogenous Leukemia (CML): Result from translocation between chromosomes $22$ and $9$.
      - Burkett Lymphoma: Result from translocation between a portion of chromosome $8$ and $14$.

Conclusion

• Understanding the structure, replication, and maintenance of DNA is crucial for comprehending genetics and the implications of mutations and alterations thereof.

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