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Central Dogma of Molecular Biology

Defined as the directional flow of genetic information: DNA to Transcription to mRNA to Translation to Protein.

Overview: DNA to Pre-mRNA to Mature mRNA to tRNA, Ribosomes, and Enzymes, to Protein.

Step 1: Transcription. DNA to RNA, in the Nucleus. Transcription is the process of copying the genetic information of a gene from a DNA template strand into a complementary sequence of RNA.

  1. Initiation: First, Promoter Recognition: RNA polymerase binds to the promoter, a leader sequence upstream of the gene called TATATA or TATAAA. Second, Unwinding: RNA polymerase locally unzips and unwinds the DNA double helix.

  2. Elongation: First, Reading and Synthesis: RNA polymerase reads the template strand and synthesizes a complementary, single-stranded pre-mRNA. Second, Base Pairing Rules: A-U, C-G pairs; The non-template DNA strand is the sense, or coding strand, because its sequence matches the resulting mRNA.

  3. Termination: RNA polymerase rewinds the DNA helix behind it. It reaches a terminator sequence to end of the gene, detaches, and releases the new pre-mRNA.

Step 2: Modification. Pre-mRNA Splicing, Location: Nucleus. Before leaving the nucleus, pre-mRNA is heavily edited to become functional, mature mRNA:

  1. Excision and Splicing: First, Introns: Non-coding introns of pre-mRNA are cut out and discarded. Second, Exons: The functional, protein-coding portions are spliced together.

  2. Alternative Splicing: Pre-mRNA can be cut and spliced into multiple different combinations of exons. One gene can code for more than one protein.

  3. Export: Mature mRNA exits the nucleus through nuclear pores into the cytoplasm.

Step 3: Translation. RNA to Protein, Location: free ribosomes or RER. Translation converts the nucleotide sequence of mRNA into a corresponding sequence of amino acids. It proceeds through three stages:

  1. Initiation The small ribosomal subunit binds and slides along RNA until it encounters the start codon: AUG. tRNA carrying anticodon UAC with the amino acid methionine pairs with the AUG codon. The large ribosomal subunit docks over the complex, locking tRNA into P site.

  2. Elongation: The 3-Site Cycle Elongation repeats in a cyclic three-step mechanism: First, Codon Recognition, A site: The next tRNA carrying its amino acid binds to the mRNA codon in the A site. Second, Peptide Bond Formation: An enzyme from the large ribosomal subunit catalyzes the formation of a peptide bond, transferring the growing polypeptide chain from the tRNA in the P site to the amino acid on the tRNA in the A site. Third, Translocation, A to P to E: The ribosome moves to the next codon. The P site tRNA shifts to the E, or exit site, and is ejected to be recharged with another amino acid. The tRNA holding the peptide chain shifts from the A to the P, leaving the A open to next codon-anticodon match.

  3. Termination Elongation continues until a stop codon—UAA, UAG, or UGA—arrives in the A site. No tRNA matches a stop codon; instead, a release factor binds to A. The release factor prompts the hydrolysis of the bond between the polypeptide and the last tRNA, freeing the newly completed protein. The ribosome breaks down to small and large subunits.

Step 4: Post-Translational Modification and Sorting

  1. Proteins Folding Chaperones prevent misfolding and guide proteins into their proper spatial structures, secondary and tertiary conformations.

  2. Destination Routing From Free Ribosomes: some proteins stay inside the cell for intracellular functions. From Rough ER and Golgi Complex: Proteins are transported into the Rough ER for carbohydrate additions, then to the Golgi Complex for sorting, further trimming, and packaging into secretory vesicles or lysosomes; some of them will be exocytosized outside of the cell.

Cell Cycle: Interphase and Mitosis

Interphase: Preparation G1, First Gap Phase: Cell growth, accumulate materials for DNA replication. S, Synthesis Phase: Semi-conservative DNA replication occurs, forming paired sister chromatids. Duplicates centrioles. G2, Second Gap Phase: Growth, preparation for division, and double-checking DNA for replication errors. Synthesis enzymes that control cell division. G0: Some cells left the cycle for a rest, like muscle and nerve cells.

Mitosis, PMAT, and Cytokinesis Prophase: Chromosomes shorten and thicken coiling into compact rods, nucleolus disappears, and nuclear envelope breaks down. Metaphase: Chromosomes are aligned on the cell equator. Anaphase: Centromeres divide and sister chromatids pull apart to opposite poles. Telophase: Reverse of prophase; chromosomes uncoil and new nuclear envelopes form. Cytokinesis: Cytoplasm divided into two identical daughter cells.

DNA Replication Steps DNA replication follows the law of complementary base pairing and the steps below:

Step 1: Initiation, Unwinding, and Fork Stabilization The double helix unwinds from histones. DNA helicase: opens one short segment of the helix, exposing the nitrogenous bases, forming a replication fork. DNA gyrase: removes torsional strain introduced by opening double helix. SSB proteins: stabilize unwound DNA.

Step 2: Leading Strand Elongation, Continuous Synthesis The leading strand parental template: runs 3-prime to 5-prime toward the advancing replication fork. RNA primase: places a single RNA primer at the origin. DNA polymerase III: synthesize a DNA strand in 5-prime to 3-prime direction toward the opening fork. Synthesis proceeds without interruption to form a single continuous strand.

Step 3: Lagging Strand Elongation, Discontinuous Synthesis The opposing lagging strand template runs 5-prime to 3-prime toward the fork, forcing synthesis to move backward, 5-prime to 3-prime away from the fork. Helicase: opens short segments. RNA primase: places fresh RNA primers near the advancing fork. DNA polymerase III: synthesize new segments from primer backward away from the fork until it reaches the preceding primer. The segments are called Okazaki fragments. Repetition of this cycle yields a segmented ladder of Okazaki fragments along lagging strand.

Step 4: Primer Removal, Gap Filling, and Backbone Ligation DNA polymerase I: detects and removes primers via exonuclease activity and replaces them with DNA nucleotides. DNA Ligase: creates a phosphodiester bond between Okazaki fragments on lagging strand and consumes ATP in this step.

Step 5: Proofreading and Quality Control DNA polymerase III made mistakes. DNA polymerase II scans the entire DNA for mistakes. DNA polymerases then double check the new base pair and replace incorrect, unstable pairs with more stable correct pairs. The finished process generates two identical double-stranded daughter DNA molecules, each containing one conserved parental strand and one newly synthesized strand, known as semiconservative replication.

Step 6: Helix Forming Histones are synthesized in the cytoplasm and are transported into the nucleus after DNA replication. Each new DNA helix wraps around them to make new nucleosomes.