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Nucleic Acids The nucleic acids DNA and RNA consist of monomers called nucleotides that consist of a • Pentose sugar. • Nitrogen-containing base. • Phosphate. nucleotide Nitrogen Bases The nitrogen bases in DNA and RNA are • Pyrimidines C, T, and U • Purines A and G. Pentose Sugars The pentose (five-carbon) sugar • In RNA is ribose. • In DNA is deoxyribose with no O atom on carbon 2’. • Has carbon atoms numbered with primes to distinguish them from the atoms in nitrogen bases. Nucleosides A nucleoside • Has a nitrogen base linked by a glycosidic bond to C1’ of a sugar (ribose or deoxyribose). • Is named by changing the the nitrogen base ending to • -osine for purines and -idine for pyrimidines. HO Nucleotides A nucleotide • Is a nucleoside that forms a phosphate ester with the C5’ –OH group of a sugar (ribose or deoxyribose). • Is named using the name of the nucleoside followed by 5’-monophosphate Nucleosides and Nucleotides with Purines Nucleosides and Nucleotides with Pyrimidines Primary Structure of Nucleic Acids Structure of RNA The primary structure of RNA • Is a single strand of nucleotides. • Consists of the bases A, C, G, and U linked by 3’-5’ ester bonds between ribose and phosphate. Structure of DNA In the primary structure of DNA, A, C, G, and T are linked by 3’-5’ ester bonds between deoxyribose and phosphate. Data of Erwin Chargaff Organism %A %T %C %C A/T G/C Maize Octopus Chicken Human Rat Wheat E.coli X174 26.8 33.2 28.0 29.3 28.6 27.3 24.7 24.0 27.2 31.6 28.4 30.0 28.4 27.1 23.6 31.2 22.8 17.6 22.0 22.0 22.0 22.0 22.0 22.0 23.2 17.6 21.6 20.0 20.5 22.8 25.7 21.5 1.0 1.1 1.0 1.0 1.0 1.0 1.1 0.8 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.1 Chargaff’s Rules: %A = %T; %G = %C X–Ray Diffraction Pattern of DNA Helical Cross DNA Secondary Structure Double Helix DNA Replication Watson-Crick Idea “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Watson, J.D and F.H.C. Crick Nature 171, 737-738 (1953) DNA Replication DNA Replication Transcription: DNA to RNA Transcription of mRNA tRNA Structure Induction of genes normally repressed (Inducer) Negative Regulation (bound repressor + corepressor inhibits transcription) Repression of genes normally expressed corepressor Posttranscriptional Processing of mRNA Genetic Code Protein Synthesis Amino Acid Activation Transfer energized amino acid to its specific tRNA. Energize the amino acid. Costs equivalent to 2 ATP. Protein Synthesis Translation Protein Synthesis: Role of Polysomes Antibiotics: Inhibitors of Protein Synthesis Streptomycin: inhibits initiation and causes misreading of the genetic code Tetracyclines: inhibit binding of aa-tRNA Chloramphenicol: inhibits peptide bond formation Erthromycin: inhibits translocation Mutations Recombinant DNA Polymerase Chain Reaction (PCR) 3’ 5’ Third Cycle Second Cycle First Cycle 5’ 3’ heat to separate the two strands add primers, cool to 55oC use DNA polymerase, to extend chains heat to separate the two strands heat to separate the two strands add primers, cool to 55oC use DNA polymerase, to extend chains add primers, cool to 55oC use DNA polymerase, to extend chains DNA Fingerprinting Retrovirus Action AIDS Virus and Treatment Examples of protease inhibitors: saquinavir, indinavir, ritonavir Examples of non-nucleoside reverse transcriptase inhibitors: etravirine, efavirenz, nevirapine AZT (3’-azido-3’deoxythymidine) (nucleoside analog reverse transcriptase inhibitor)