Frederick Griffith (1928): Mixed heat-killed S-strain + live R-strain of Streptococcus pneumoniae → mice died. Proved existence of a heritable "transforming principle."

Avery, MacLeod, McCarty (1944): Only DNase treatment destroyed the transforming principle → DNA is the genetic material. Protease and RNase had no effect.

Hershey and Chase (1952): Used bacteriophage T2 with ^32P-labelled DNA and ^35S-labelled protein. After infection: ^32P in bacterial pellet → DNA enters bacteria. ^35S in supernatant → protein stays outside. DNA = genetic material.

Watson and Crick (1953): Proposed the right-handed double helix model based on X-ray data (Franklin, Wilkins) and Chargaff's base-pairing rules. Two antiparallel strands; complementary bases; sugar-phosphate backbone.

Chargaff's Rules: In any dsDNA: A = T and G = C. Purines = Pyrimidines. $\frac{A+G}{(T+C)}$ = 1.0 always. Applies ONLY to double-stranded DNA.

Base Pairing: A=T (2 hydrogen bonds); G≡C (3 hydrogen bonds). GC-rich DNA is more thermally stable.

Nucleosome: ~200 bp DNA wrapped around histone octamer (2×H2A, 2×H2B, 2×H3, 2×H4). H1 is the LINKER histone (NOT in octamer). Fundamental unit of chromatin.

Chromatin levels: DNA → 11 nm beads on string → 30 nm solenoid → loops → 300 nm → metaphase chromosome.

Antiparallel nature of DNA is essential for base pairing and explains directionality of synthesis in replication and transcription.