Biology Chapter: DNA Structure and Organization

Levels of Organization

• Nucleosomes: DNA coiled around a core of eight histone proteins, forming a "beads on a string" structure.
• Chromatin Types:
  • Euchromatin: Less condensed, actively involved in transcription and gene expression, representing about 90% of the human genome.
  • Heterochromatin: Highly condensed, generally transcriptionally inactive. Two types:
    • Constitutive heterochromatin: Always condensed, contains few genes.
    • Facultative heterochromatin: Can transition between condensed and less condensed states based on gene expression needs.
• Chromosome Structure: During cell division, chromatin condenses to form visible chromosomes. Each chromosome consists of two sister chromatids joined at the centromere.

Discovery of DNA

• Friedrich Miescher (1869): Discovered "nuclein" (DNA).
• Oswald Avery (1944): Demonstrated DNA is the substance responsible for heredity, transforming non-virulent bacteria into virulent ones.
• Erwin Chargaff (1940s): Formulated Chargaff's rules: Adenine (A) pairs with Thymine (T) and Cytosine (C) pairs with Guanine (G).
• Rosalind Franklin (1952): Used X-ray diffraction to capture images of DNA, revealing its helical structure.
• James Watson and Francis Crick (1953): Proposed the double-helix model of DNA, incorporating findings from previous researchers.

DNA Structure

• Double Helix: Two strands of DNA wind around each other.
• Nucleotides: Each strand is composed of alternating sugar (deoxyribose) and phosphate groups, with a nitrogenous base attached to each sugar.
• Base Pairs:
  • Adenine (A) pairs with Thymine (T) (two hydrogen bonds).
  • Cytosine (C) pairs with Guanine (G) (three hydrogen bonds).

DNA Replication

• Origin of Replication: Specific sequence where DNA replication begins. Prokaryotes have one origin, while eukaryotes have multiple.
• Semi-conservative Replication: Each new DNA molecule has one original strand and one newly synthesized strand.
• Key Enzymes:
  • Helicase: Unwinds the DNA double helix, separating the strands.
  • Single-Strand Binding Proteins (SSBPs): Prevent separated strands from re-annealing.
  • Topoisomerase: Relieves tension ahead of the replication fork by cutting and rejoining DNA strands.
  • Primase: Synthesizes short RNA primers, providing a starting point for DNA polymerase.
  • DNA Polymerase: Synthesizes new DNA strands by adding nucleotides complementary to the template strand.

The Lac Operon

• Negative Regulation by Lac Repressor:
  • In the absence of lactose, the lac repressor binds to the operator, blocking RNA polymerase from transcribing the lac operon.
  • With lactose present, allolactose (an inducer) binds to the repressor, causing it to detach from the operator, allowing transcription to occur.
• Positive Regulation by CAP:
  • When glucose is scarce, cAMP levels rise. cAMP binds to CAP, which in turn binds to the CAP-binding site, enhancing RNA polymerase binding and increasing transcription.
  • When glucose is abundant, cAMP levels decrease, CAP doesn't bind, reducing transcription.
• Dual Regulation:
  • The lac operon is most active when lactose is present and glucose is absent.
  • When glucose is available, it is preferentially utilized, and the lac operon remains minimally expressed until glucose is depleted (catabolite repression).

The Epigenome

• Chemical Modifications and Markers: The epigenome regulates gene activity and expression without altering DNA sequence.
• Key Components:
  • DNA Methylation: Addition of a methyl group (CH₃) to DNA, typically at cytosine bases in CpG dinucleotides. Usually represses gene expression.
    • Plays a role in X-chromosome inactivation, genomic imprinting, and silencing transposable elements.
  • Histone Modifications: Modifications to the histone proteins around which DNA is wrapped. Can alter chromatin structure and accessibility for transcription factors.
    • Play a role in regulating gene expression, DNA replication, and repair.

Harmful Mutations

• Can disrupt normal cell regulation and growth, potentially leading to genetic disorders or contributing to diseases like cancer.

Conclusion

• The study of genes and genomes is crucial for advancements in biotechnology and for understanding biological processes.
• Understanding DNA replication, transcription, translation, and gene regulation is essential for developing biotechnological applications and addressing genetic disorders.

DNA vs. RNA

• Structure: DNA is double stranded, RNA is single stranded.
• Sugar: DNA contains deoxyribose, RNA contains ribose.
• Bases: DNA has Adenine (A), Thymine (T), Cytosine (C), and Guanine (G). RNA has Adenine (A), Uracil (U), Cytosine (C), and Guanine (G).
• Function: DNA stores genetic information, RNA is involved in protein synthesis and gene regulation.
• Location: DNA is primarily found in the nucleus (eukaryotes) or the nucleoid region (prokaryotes). RNA is found in the nucleus, cytoplasm, and ribosomes.
• Stability: DNA is more stable due to its double-stranded structure. RNA is less stable and more prone to degradation.
• Replication: DNA is self-replicating. RNA is synthesized from DNA during transcription.
• Types: DNA has one main type. RNA has three main types: mRNA, rRNA, and tRNA.

mRNA vs. rRNA vs. tRNA

• mRNA (Messenger RNA): Carries genetic information from DNA to ribosomes for protein synthesis.
• ** rRNA (Ribosomal RNA):** Forms the core component of ribosomes and catalyzes protein synthesis.
• tRNA (Transfer RNA): Transfers specific amino acids to the ribosome during translation.

Types of DNA

• Genomic DNA: The complete set of DNA, including all genes and non-coding sequences.

Explore the intricate levels of organization within DNA, including nucleosomes and the two types of chromatin: euchromatin and heterochromatin. Learn about the remarkable history of DNA discovery, from Friedrich Miescher's identification of nuclein to Oswald Avery's pivotal experiments demonstrating DNA's role in heredity.