Nucleic acids were first isolated by Friedrich Miescher in 1869. Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) The monomers constituting nucleic acid polymers are nucleotides:
“Transforming principle” of pneumonia-causing bacteria (Griffith, 1928) DNA is the “transforming principle” (Avery, McLeod and McCarty, 1944) “Waring Blender Experiment” (Hershey and Chase, 1952) DNA is the Genetic Material
Avery, McLeod and McCarty, 1944
“Waring Blender Experiment” (Hershey and Chase, 1952)
Three-Dimensional Structure of Deoxyribonucleic Acid (DNA) Double Helix: 50 Years of DNA http://www.nature.com/nature/dna50/
An Early Conjecture about DNA Structure Tetranucleotide hypothesis (Levene, 1910)
X-Ray Diffraction Pattern of DNA Fibers Franklin and Wilkins, 1953 Rosalind Franklin Maurice Wilkins
X-Ray Diffraction Pattern of DNA Fibers Franklin and Wilkins, 1953
Incorrect Triple-Helical Structure Pauling and Corey, 1953
April 25, 1953 MOLECULAR STRUCTURE OF NUCLEIC ACIDS A Structure for Deoxyribose Nucleic Acid We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest. … It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material. … J. D. WATSON F. H. C. CRICK Medical Research Council Unit for the Study of Molecular Structure of Biological Systems, Cavendish Laboratory, Cambridge.
The A, B and Z Forms of DNA • Most DNA in the cell is in the B form. A small amount of the DNA in the cell may locally adopt the Z conformation (where sequence has alternating purine and pyrimidine bases). The A form of DNA is found in dehydrated samples of DNA but not normally in the cell. However, double-stranded RNA and DNA-RNA hybrids form helices resembling the A form of DNA.
Z-DNA: Left-Handed Helix Alexander Rich, 1979
Proteins that Bind Z-DNA X-Ray structure of two ADAR1 Z domains in complex with Z-DNA.
Nucleotide Conformation Sugar-phosphate backbone is conformationally constrained (O4’ generally gauche to O5’ since torsion angle about the C4’-C5’ bond is restricted).
Sugar Conformation In A-DNA: sugar pucker is C3’-endo. In B-DNA: C2’-endo. In Z-DNA: pyrimidines are C2’-endo, but purines are C3’-endo.
Orientation of Bases with Respect to Sugar In A- and B-DNA, all bases are in anti orientation. In Z-DNA, pyrimidines are anti, but purines are syn.
Properties of Naturally Some Occurring DNA Molecules Haploid human genome: 23 chromosomes of ~5 × 107 bp to ~25 × 107 bp each for a total of ~3 × 109 bp.
Genetic Information Flow: DNA RNA Protein“The Central Dogma”Francis Crick, 1957
Replication, Transcription and Translation Replication and transcription occur in the nucleus Translation occurs in the cytoplasm
Hydrolysis of Pyrophosphate DGo’= -33.5 kJ/mol
Gene Expression (Transcription, Splicing and Translation) Expression of a hypothetical eukaryotic gene