Molecular Biology & Genetics Fundamentals

MolBio integrates biochem, genetics, and cell bio to explain how living systems store, transmit, and express genetic information at the molecular level.

## DNA Structure & Replication

DNA double helix: antiparallel strands connected by H-bonds between complementary bases — A=T (2 H-bonds), G≡C (3 H-bonds). Sugar-phosphate backbone w/ 3'→5' phosphodiester bonds. B-form DNA: 10 bp per turn, 3.4 nm pitch, 2 nm diameter. Major groove (protein binding, TF recognition) and minor groove.

Replication is semiconservative (Meselson-Stahl experiment). Origin of replication (ORI): prokaryotes have 1 (oriC), eukaryotes have many. Helicase unwinds, SSB proteins stabilize, topoisomerase relieves torsional strain. Primase synthesizes RNA primer. DNA Pol III (prokaryotes) or Pol δ/ε (eukaryotes) extends 5'→3' only.

Leading strand: continuous synthesis toward replication fork. Lagging strand: discontinuous Okazaki fragments (100-200 nt in eukaryotes, 1000-2000 in prokaryotes). DNA Pol I removes RNA primers and fills gaps. DNA ligase seals nicks. Proofreading: 3'→5' exonuclease activity of DNA Pol, error rate ~10⁻⁷ per bp after MMR.

Telomeres: TTAGGG repeats (human) at chromosome ends, shortened each division (end replication problem). Telomerase (reverse transcriptase + RNA template) extends telomeres — active in stem cells and cancer cells, silenced in most somatic cells. Telomere shortening → replicative senescence → Hayflick limit (~50 divisions).