13.2 Central Dogma of Molecular Biology

The Central Dogma of Molecular Biology explains how genetic info flows from DNA to RNA to proteins. It's the backbone of modern genetics, showing how our genes make the molecules that run our bodies. This concept revolutionized our understanding of life.

Understanding the Central Dogma is key to grasping DNA's role in life. It's led to breakthroughs in medicine, helping us fight diseases and develop new treatments. This idea changed how we see genes and their impact on our health.

Central Dogma of Molecular Biology

Overview of the Central Dogma

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• The central dogma of molecular biology describes the flow of genetic information from DNA to RNA to proteins, the main functional molecules in cells
• The three key processes involved in the central dogma are replication, transcription, and translation
• The central dogma is a unidirectional process, with information flowing from DNA to RNA to proteins, but not in the reverse direction
• Exceptions to the central dogma include reverse transcription in retroviruses (HIV) and direct translation from DNA to protein in some viruses (Hepatitis B)

Importance of the Central Dogma

• The central dogma provides a framework for understanding how genetic information is stored, transmitted, and expressed in living organisms
• It explains the relationship between genes, RNA, and proteins, which are essential for cellular function and the development of complex traits
• Understanding the central dogma is crucial for advancements in fields such as molecular biology, genetics, biotechnology, and medicine (personalized medicine, gene therapy)
• Disruptions in the processes of the central dogma can lead to various genetic disorders (sickle cell anemia) and diseases (cancer)

DNA Replication and Genetic Integrity

Mechanism of DNA Replication

• DNA replication is the process by which a cell duplicates its entire genome before cell division, ensuring that each daughter cell receives an identical copy of the genetic material
• Replication begins at specific sites called origins of replication and proceeds bidirectionally, creating two replication forks
• The enzyme DNA helicase unwinds the double-stranded DNA, separating the two strands to form a replication bubble
• Single-stranded DNA binding proteins stabilize the separated single strands of DNA
• DNA primase synthesizes short RNA primers complementary to the single-stranded DNA, providing a starting point for DNA synthesis
• DNA polymerase III extends the primers, synthesizing the new DNA strands in the 5' to 3' direction
  • The leading strand is synthesized continuously, while the lagging strand is synthesized discontinuously as Okazaki fragments
• DNA polymerase I replaces the RNA primers with DNA nucleotides, and DNA ligase joins the Okazaki fragments to create a continuous strand

Maintaining Genetic Integrity

• Accurate DNA replication is crucial for maintaining genetic integrity and preventing mutations that can lead to genetic disorders (Down syndrome) or cancer
• DNA polymerases have proofreading activity, which allows them to correct errors during replication
• Telomerase, a specialized RNA-dependent DNA polymerase, maintains the telomeres at the ends of linear chromosomes to prevent loss of genetic information during replication
• DNA repair mechanisms, such as mismatch repair, base excision repair, and nucleotide excision repair, fix damage or errors in the DNA sequence
• Checkpoints in the cell cycle ensure that DNA replication is complete and accurate before the cell proceeds to division (mitosis or meiosis)

Transcription and RNA's Role in Gene Expression

Mechanism of Transcription

• Transcription is the process by which the genetic information in DNA is copied into a complementary RNA sequence
• Transcription is catalyzed by the enzyme RNA polymerase, which synthesizes RNA from a DNA template
• Transcription occurs in three stages: initiation, elongation, and termination
  • During initiation, RNA polymerase binds to a promoter sequence on the DNA and separates the two strands to form a transcription bubble
  • In elongation, RNA polymerase moves along the DNA template, synthesizing the RNA strand in the 5' to 3' direction by adding ribonucleotides complementary to the DNA sequence
  • Termination occurs when RNA polymerase encounters a termination signal, releasing the newly synthesized RNA and dissociating from the DNA template
• The primary transcript undergoes post-transcriptional modifications, such as 5' capping, 3' polyadenylation, and splicing (in eukaryotes) to produce a mature mRNA

RNA's Roles in Gene Expression

• RNA plays a crucial role in gene expression by serving as a template for protein synthesis (mRNA)
• RNA also has regulatory functions, such as microRNA (miRNA) and small interfering RNA (siRNA), which can silence gene expression post-transcriptionally
• Some RNA molecules, called ribozymes, have catalytic functions and can perform enzymatic reactions (self-splicing introns)
• Ribosomal RNA (rRNA) and transfer RNA (tRNA) are essential components of the translation machinery
• Long non-coding RNAs (lncRNAs) are involved in various cellular processes, including transcriptional regulation, chromatin remodeling, and nuclear organization

Translation and Protein Synthesis from mRNA

Mechanism of Translation

• Translation is the process by which the genetic information encoded in an mRNA molecule is used to synthesize a polypeptide chain
• Translation occurs in the cytoplasm of a cell and involves ribosomes, tRNAs, and various protein factors
• The mRNA sequence is read in triplets called codons, each coding for a specific amino acid or serving as a stop signal
• tRNAs act as adaptor molecules, carrying specific amino acids and having anticodon sequences complementary to the codons on the mRNA
• Translation occurs in three stages: initiation, elongation, and termination
  • During initiation, the small ribosomal subunit binds to the start codon (AUG) on the mRNA, and the initiator tRNA carrying methionine is recruited
  • In elongation, the large ribosomal subunit joins, and the ribosome moves along the mRNA, with tRNAs bringing in the corresponding amino acids. Peptide bonds are formed between the amino acids, creating a growing polypeptide chain
  • Termination occurs when the ribosome encounters a stop codon (UAA, UAG, or UGA). Release factors bind to the stop codon, triggering the release of the completed polypeptide chain and the dissociation of the ribosome

Post-translational Modifications and the Genetic Code

• The newly synthesized polypeptide chain undergoes post-translational modifications, such as folding, cleavage, and the addition of functional groups, to form a mature, functional protein
• Examples of post-translational modifications include phosphorylation, glycosylation, and disulfide bond formation
• The genetic code is nearly universal across all life forms, with a few exceptions in some organelles (mitochondria) and microorganisms (mycoplasma)
• The genetic code is degenerate, meaning that multiple codons can code for the same amino acid (synonymous codons)
• The universality of the genetic code allows for the expression of genes from one organism in another (recombinant DNA technology)