Nucleic Acids

Nucleic Acids and Protein Synthesis

6.1 Structure and Replication of DNA

  • Nucleotides: Basic units of DNA and RNA, linked to form polynucleotides.

    • Related to the structure of nucleic acids, nucleotides consist of a phosphate group, a five-carbon sugar (deoxyribose in DNA and ribose in RNA), and a nitrogenous base.

  • Purines: Larger, double-ringed molecules (e.g., adenine, guanine).

  • Pyrimidines: Smaller, single-ringed molecules (e.g., thymine, cytosine, uracil).

  • Covalent Bonds: Nucleotides in DNA and RNA are linked by phosphodiester bonds, which create a sugar-phosphate backbone and establish the overall structural integrity.

  • Location: DNA synthesis occurs in the nucleus during interphase, ensuring genetic information is replicated before cell division.

Structure of DNA

  • DNA Ladder:

    • Sides: Alternating phosphate and deoxyribose molecules create the backbone of the DNA molecule.

    • Rungs: Nitrogenous bases linked by hydrogen bonds form pairs (A-T and C-G).

    • Strands: DNA is composed of 2 anti-parallel polynucleotide strands held together by hydrogen bonds, exhibiting a double helical structure that is crucial for its stability and function.

Semi-Conservative Replication of DNA

  1. Unwinding DNA:

    • Enzyme helicase unwinds the double helix by splitting hydrogen bonds, creating a replication fork, allowing access to both strands for synthesis.

  2. Primer Synthesis:

    • Enzyme primase synthesizes short RNA primer to start new strand synthesis, necessary for initiation due to DNA polymerase's requirement for a primer.

  3. Strand Synthesis:

    • Enzyme DNA polymerase adds nucleotides in a 5' to 3' direction. Continuous synthesis occurs on the leading strand; the lagging strand is synthesized in Okazaki fragments, requiring multiple primers and synthesis events.

  4. Sealing Fragments:

    • DNA ligase seals Okazaki fragments to create a continuous double-stranded helix, ensuring the integrity and fidelity of the genetic material.

6.2 Protein Synthesis

  • Polypeptides: Coded for by genes, which are sequences of nucleotides in DNA that encode specific proteins.

  • Codon: Sequence of 3 nucleotide bases coding for one amino acid, establishing the sequence of the polypeptide chain.

  • Gene Mutation: Change in nucleotide sequence, resulting in altered polypeptides. Types include theft of base pairs through:

    • Substitution: Replace one base with another.

    • Deletion: Remove a base.

    • Insertion: Add a base.

    • Inversion: Reverse the sequence.

    • Frameshift: Change the reading frame, affecting the entire sequence downstream.

  • Alleles: Variants of genes caused by mutations, contributing to genetic diversity. Example: Sickle cell anemia caused by substitution mutation: adenine replaces thymine in the triplet CTT (CAT instead), resulting in valine (GTG) rather than glutamic acid (GAG).

Protein Folding

  • Folding Process:

    • Newly synthesized polypeptides undergo folding to achieve their final three-dimensional conformation, which is critical for their function.

    • Chaperone Proteins: Assist in the correct folding of polypeptides by preventing aggregation and facilitating the proper conformation, which is essential for functional active sites.

    • Levels of Organization: Folding occurs in several stages:

      • Primary Structure: Sequence of amino acids in a polypeptide chain.

      • Secondary Structure: Local folding into alpha-helices or beta-pleated sheets due to hydrogen bonding.

      • Tertiary Structure: The overall three-dimensional shape formed by further folding and interactions between side chains.

      • Quaternary Structure: Assembly of multiple polypeptide chains into a functional protein complex.

Protein Synthesis Process

a) Transcription

  • Process of creating mRNA from a DNA template.

    • Binding: RNA polymerase binds to the promoter region, signaling DNA unwinding and initiating transcription.

    • Reading Direction: RNA polymerase reads the sense strand in a 3' to 5' direction, synthesizing mRNA in a 5' to 3' direction.

    • Termination: Occurs at the terminator sequence; RNA polymerase detaches, and the DNA rewinds.

    • Stop Codons: Specific codons signal the end of transcription, including ATT, ATC, ACT in DNA (UAA, UGA, UAG in RNA).

b) Translation

  • Process by which mRNA is used to synthesize proteins.

    • mRNA Binding: mRNA leaves the nucleus and binds to the ribosomal unit, where translation occurs.

    • Codon-Anticodon Matching: Each codon specifies an anticodon carried by tRNA, which is covalently linked to an amino acid.

    • 64 possible codons for 20 amino acids; special codon AUG serves as START, marking the beginning of translation.

    • Initiation: Initiator tRNA binds to START codon, positioning on the ribosome.

    • Amino Acid Linking: The next tRNA enters carrying an amino acid that covalently binds to the first.

    • Continuation: The process repeats, elongating the polypeptide until a stop codon is reached, culminating translation and the formation of the final protein product.