DNA and RNA

Definition of Nucleic Acids: Nucleic acids are large biomolecules, essential for all known forms of life. They are composed of nucleotide units which contain a nitrogenous base, a sugar molecule, and a phosphate group.
- Nucleotides: Comprised of a phosphate group, a sugar (deoxyribose in DNA and ribose in RNA), and a nitrogenous base (either purine or pyrimidine).
- Purines: Adenine (A) and Guanine (G).
- Pyrimidines: Cytosine (C), Thymine (T, only in DNA), and Uracil (U, only in RNA).
- Pairings: A pairs with T (or U in RNA) and G pairs with C based on Chargaff's rule; A = T and G = C, reflecting complementary base pairing.

Location of Replication in the Cell Cycle:
- S Phase: Synthesis phase of the cell cycle where DNA replication occurs, positioned between G1 (gap 1) and G2 (gap 2).
- Purpose: To ensure that each daughter cell receives an exact copy of the genetic material.

Semi-Conservative Replication: This model suggests that each strand of the original double helix serves as a template for the new strand. After replication, each new double helix consists of one old (template) strand and one newly synthesized strand.
Hydrogen Bonding: G-C pairs form three hydrogen bonds while A-T pairs form two, ensuring stability and consistency in distance between base pairs.

Anti-Parallel Orientation: The two strands of DNA run in opposite directions; one runs 5' to 3' and the other 3' to 5'.
Components of DNA Backbone: Composed of alternating phosphate and sugar (deoxyribose) units, linked by phosphodiester bonds.
- 5' and 3' Ends: Phosphate attaches to the 5' carbon of one sugar and connects to the 3' carbon of the next sugar, allowing for unidirectional synthesis during replication.

Strand Separation: Utilizes helicase to unwind the double helix at specific origins of replication, creating replication bubbles.
- Single-Stranded Binding Proteins (SSBPs): Prevent re-annealing of DNA strands.
- Topoisomerase: Relieves the tension in the DNA strand ahead of the replication fork by cutting, twisting, and rejoining DNA strands.
Primer Synthesis:
- Primase: An enzyme that synthesizes a short RNA primer that provides a starting point for DNA polymerase, which cannot initiate synthesis without a primer.
DNA Synthesis:
- DNA Polymerase III: Responsible for adding nucleotide bases complementary to the template strand in the 5' to 3' direction.
- Leading Strand vs. Lagging Strand: The leading strand is synthesized continuously while the lagging strand is synthesized in short segments known as Okazaki fragments.
  - Okazaki Fragments: These are short sections of DNA created on the lagging strand that need to be later joined together.
Primer Replacement and Strand Joining:
- DNA Polymerase I: Removes the RNA primer from the lagging strand and fills in the gap with DNA nucleotides.
- DNA Ligase: Joins Okazaki fragments together by forming phosphodiester bonds, effectively sealing the nicks between the fragments to create a continuous DNA strand.

DNA Polymerase Fidelity: DNA polymerase has a proofreading ability that decreases the error rate to roughly one mistake in a billion bases added.
Excision Repair Mechanism: Nucleases cut out damaged sections, and DNA polymerase fills in the missing pieces, followed by ligase sealing the backbone.

Role of Telomeres: Protect chromosome ends from degradation during replication. Telomeres shorten with each round of DNA replication, contributing to cellular aging and limits on cell division.
Telomerase: Enzyme that adds repetitive sequences to telomeres, which maintains their length in certain cells (like stem cells) to prevent aging.

Mutation Rates: Despite accurate mechanisms, mutations still occur with rates in the order of one in 10,000 to one in 50,000 base pairs due to replication errors.
Consequences of Mutations: Specific mutations can lead to genetic disorders such as cystic fibrosis or sickle cell anemia based on single nucleotide changes.

Importance of Accurate DNA Replication: High fidelity in DNA replication is crucial because errors can lead to significant health issues, including cancer, which occurs when the regulation and repair mechanisms fail.