DNA Structure and Expression Overview

DNA Structure

DNA consists of two long strands that twist around each other, forming a structure known as a double helix, which resembles a twisted ladder. This helical structure is crucial for the functionality and stability of DNA. Each DNA strand is made of smaller units called nucleotides, which have three components:

• Phosphate Group: Links one nucleotide to another, forming the backbone of the DNA strand.

• Sugar: The sugar in DNA is known as Deoxyribose, providing structural integrity and stability.

• Nitrogenous Base: These bases are categorized into two groups:

  • Purines: Larger, two-ring structures consisting of Adenine (A) and Guanine (G).

  • Pyrimidines: Smaller, single-ring structures made of Cytosine (C) and Thymine (T).

Base Pairing

The nitrogenous bases pair specifically through hydrogen bonds, which stabilize the double helix:

• Adenine (A) pairs exclusively with Thymine (T) via two hydrogen bonds.

• Guanine (G) pairs exclusively with Cytosine (C) through three hydrogen bonds.
  This specific base pairing is essential for precise DNA replication and maintaining genetic fidelity.

DNA Packaging

Human DNA is approximately 1.8 meters in length but is extremely compact, measuring about 0.09 micrometers in width. To achieve this compactness, DNA is wrapped around proteins known as histones, forming structural units called nucleosomes. Nucleosomes further coil and stack to create higher-order structures called chromatin, enabling efficient storage and organization of genetic material within the nucleus.

DNA Damage and Repair

Each cell encounters 1,000 to 1 million instances of DNA damage daily due to environmental factors like UV radiation and normal metabolic processes. Cells possess robust DNA repair mechanisms, including:

• Nucleotide Excision Repair: Identifies and repairs bulky DNA lesions.

• Base Excision Repair: Rectifies damaged nitrogenous bases, preserving the integrity of genetic information.
  These repair systems are vital to prevent mutations that may lead to diseases, such as cancer.

Nucleotides and Their Bonds

Each nucleotide's phosphate group is connected to the 5' carbon of the deoxyribose sugar. The nitrogenous base is attached to the 1' carbon of the sugar. These connections form phosphodiester bonds, which are crucial for DNA's structural integrity and stability.

Chargaff's Rules

Chargaff’s analysis revealed significant relationships among nitrogenous bases:

• Adenine (A) always equals Thymine (T) (A = T).

• Guanine (G) always equals Cytosine (C) (G = C).
  This complementarity is essential for biochemical processes like DNA replication and transcription.

DNA Location in Cells

• Eukaryotic Cells: In organisms that possess a nucleus, DNA is stored within the nucleus, allowing the separation of transcription (RNA synthesis) from translation (protein synthesis).

• Prokaryotic Cells: In prokaryotic organisms, circular DNA is located in the cytoplasm, termed the nucleoid region, which allows for rapid access to genetic material.

Gene Expression Process

1. Transcription: RNA is synthesized from a DNA template.

   • Occurs in the nucleus for eukaryotes and the cytoplasm for prokaryotes.

   • Phases include:

     • Initiation: RNA polymerase binds to the promoter region of the DNA.

     • Elongation: RNA polymerase creates an RNA strand complementary to the DNA strand.

     • Termination: The RNA strand is fully synthesized, and RNA polymerase detaches from the DNA.

2. Processing: mRNA undergoes several modifications before translation:

   • Capping: A protective 7-methylguanylate cap is added to the 5' end of the mRNA for stability.

   • Tailing: A poly-A tail made of adenine nucleotides is attached to the 3' end to prevent degradation.

   • Splicing: Non-coding regions (introns) are removed, and coding regions (exons) are joined to form a continuous sequence.

3. Translation: Proteins are synthesized using the information in mRNA, taking place in the cytoplasm at ribosomes.

   • Steps include:

     • Initiation: The ribosome binds to the mRNA at the start codon (AUG, which codes for methionine).

     • Elongation: Transfer RNA (tRNA) brings the correct amino acids to the ribosome, aligning with corresponding mRNA codons. The tRNA contains an anticodon, which is complementary to the mRNA codon.

     • Termination: Translation ceases when a stop codon (UAA, UAG, UGA) is encountered, resulting in the release of the fully formed protein.

Key Vocabulary

• Codon: A sequence of three nucleotides on mRNA that specifies a particular amino acid during protein synthesis.

• tRNA (Transfer RNA): A type of RNA that carries amino acids to the ribosome and matches them to the mRNA sequence through the complementary anticodon.

• Anticodon: A three-nucleotide sequence on tRNA that pairs with a complementary codon on mRNA.

• Transcription: The process of synthesizing RNA from a DNA template.

• Splicing: The removal of introns and joining of exons in pre-mRNA to form mature mRNA.

Overall Flow from DNA to Protein

The central dogma of molecular biology, "DNA → RNA → Protein," explains how genetic information is transcribed from DNA to RNA and then translated into functional proteins, which are essential for various biological processes and understanding genetics.

Mutations

Mutations are changes in the DNA sequence that can lead to different protein functions.

Types of Mutations:

• Point Mutations: Involve a change in a single nucleotide.

  • Can be:

    • Silent Mutations: No change in the amino acid sequence.

    • Missense Mutations: Change one amino acid in the protein sequence.

    • Nonsense Mutations: Create a premature stop codon, truncating the protein.

• Insertions: Add one or more nucleotides into the DNA sequence, potentially causing a frameshift that alters the reading frame.

• Deletions: Remove one or more nucleotides from the DNA sequence, which can also result in a frameshift mutation.

Effects of Mutations:

• Beneficial Mutations: Provide an advantage, leading to new traits or increased survival (e.g., resistance to disease).

• Harmful Mutations: Can lead to diseases or dysfunctional proteins (e.g., cancer, cystic fibrosis).

• Neutral Mutations: Have no effect on the organism's fitness.

Causes of Mutations:

• Spontaneous Mutations: Result from errors during DNA replication.

• Induced Mutations: Caused by external factors such as radiation, chemicals, or viruses.
  Understanding mutations is essential for studying genetic diversity, evolution, and the mechanisms underlying various diseases.