Central Dogma: Molecular Mechanisms of Life

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Central Dogma of Molecular Biology

The schema describes the basic functional relationships between DNA, RNA, and proteins. In essence, DNA provides a model for its own replication and transcription. RNA is translated into proteins, formed under the encoding determined by its nucleotide triplets.

Watson-Crick Hypothesis (1953)

The two strands are separated, and from each, according to the rules of base complementarity, the respective complementary strands will be constructed.

Meselson-Stahl Experiment (1957)

Bacteria are grown with N15 (heavy nitrogen) and separated by centrifugation in a medium with a density gradient.

Key Features of DNA Replication

  • It is semiconservative.
  • It is a complex process that involves many enzymes.
  • It is a two-way process.
  • It is unlike a full transcriptional process that is selective.
  • It has a single origin in prokaryotes, but in eukaryotes, there are many origins.

Enzymes Involved in DNA Replication

  • DNA polymerases: Locate the origin of replication.
  • Helicases: Separate the DNA strands.
  • Single-strand binding proteins (SSBs): Stabilize the single-stranded DNA.
  • Primase: Synthesizes RNA primers.
  • Ligase: Joins DNA fragments.
  • Gyrase (Topoisomerase): Eliminates supercoiling stress.

DNA Repair Mechanisms

Replication fidelity is essential. Although polymerases act as enzymatic complexes, there are few errors to correct, involving the removal of incorrect nucleotides and repair of alterations.

Genetic Message Expression: Transcription

Transcription is the mechanism by which a complementary nitrogenous base sequence of DNA is transcribed into an mRNA base sequence.

Stages of Transcription

  1. Initiation Phase

    RNA polymerase associates with a cofactor __, allowing it to recognize and bind to a specific region of DNA called a promoter.

  2. Elongation Phase

    RNA polymerase traverses the DNA strand at its 5' opening pattern, and an RNA strand is synthesized in the 5' → 3' direction.

  3. Termination Phase

    Release occurs upon finding the termination sequence.

  4. RNA Maturation

    The phenomenon where certain sequences are eliminated.

The Genetic Code

The genetic code establishes the relationship between nucleotide triplets and amino acid sequences. Since there are only four types of nucleotides and the correspondence involves 20 amino acids, the genetic code is based on nucleotide triplets and amino acids.

Characteristics of the Genetic Code

  1. It is universal.
  2. The coding unit is the triplet of nucleotides (codon).
  3. It is degenerate because there are several triplets for some amino acids (aa). This is an advantage because if a change occurs in one nucleotide, it could still encode the same amino acid.

Gene Regulation: The Operon Hypothesis

Case 1: Absence of Tryptophan

In the absence of tryptophan, the repressor protein does not block the promoter, allowing the expression of structural genes.

Case 2: Presence of Tryptophan

In the presence of tryptophan, it binds to the repressor protein, which then blocks the promoter, preventing RNA polymerase from transcribing.

Translation and Protein Synthesis

Translation, or protein synthesis, is the process of converting the information contained in the nucleotide sequence of mRNA into the 20 amino acids (aa) in the polypeptide structure. The process occurs in the ribosomes, involving the interaction of mRNA codons and the anticodon region of the aminoacyl-tRNA. For this, the corresponding tRNA must be united with its amino acid, a reaction catalyzed by the enzyme aminoacyl-tRNA ligase, resulting in an aminoacyl-tRNA. This reaction conserves energy from ATP. (The specificity of these enzymes is very strict).

Stages of Translation

  • Initiation of Translation

    The process involves the association of the aminoacyl-tRNA with the first codon of the mRNA, based on base complementarity. It requires initiation factors.

  • Elongation of Polypeptide Chain

    The polypeptide chain forms, extending through the formation of peptide bonds and ribosomal translocation.

  • Termination of Translation

    Upon reaching termination codons (UAA, UAG, UGA), protein factors are involved in the detachment of the polypeptide chain.

Post-Translational Protein Processing

As the polypeptide chain is synthesized, it adopts a determined spatial structure (tertiary structure) and undergoes a maturation process where some amino acids may be lost.

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