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Selected topics in molecular biology Review session Nov. 26, 2007 All nucleotides have a common structure There are five principal bases in nucleic acids Inosine is carbonylated adenosine A, G, T, C are present in DNA A, G, U, C are present in RNA UMP Conversion of ribo-to-deoxyribonucleotides 1) Ribonucleotide reductase catalyzes the synthesis of deoxyribonucleotides Inhibited by hydroxyurea, which is used as anti-cancer drug 2) Thymidylate synthase catalyzes the methylation of dUTP UMP Anti-cancer drugs specifically block dTMP production Folic acid Defects in the purine salvage pathway cause human diseases Salvage Pathway Activated ribose (PRPP) + base Blocked by HGPRT deficiency Nucleotides (Gout, Lesh-Nyhan) De Novo Pathway Activated ribose (PRPP) + amino acids + ATP + CO2 +………. Nucleotides PRPP DNA can undergo reversible strand separation Replication protein A Replication factor C The eukaryotic replication fork Inhibited by rifamycins (e.g., Rifampicin) The base pair in the 3rd codon position can “wobble” frameshift mutations Exchange of genetic material during meiosis Recombination=crossover + exchange of DNA between two DNA double strands Organization and rearrangement of heavy-chain DNA V=variable D=diversity J=joining C=constant VDJ recombination allows for antibody diversity Different classes of immunoglobulin (isotypes) fulfill different tasks 1st line of defense major class In serum major class in external secretions membranebound unknown against parasites, allergies Cell Cycle Control Multiple cdks and cyclins regulate passage of mammalian cells through the cell cycle Cdc2/Cdk1-cyclin B Cdc2/Cdk1-cyclin A Cdk4-cyclin D Cdk6-cyclin D Cdk2-cyclin A Restriction point is analogous to START Cdk2-cyclin E good genes proto-oncogenes are required for normal growth bad genes oncogenes promote uncontolled growth gain-of-function mutation (can be point mutation, insertion or deletion) tumor suppressors loss-of-function mutation inactive tumor suppressor Besides mutations in proto-oncogene/tumor suppressor coding regions, mutations in gene regulatory elements (promoter) can deregulate the expression pattern Membrane receptors and signal transduction cascades Cell-surface receptors belong to different classes G protein-coupled receptors contain 7 transmembrane alpha-helices Acetylcholine receptor in the heart muscle opens K+ channels frequency of heart contractions goes down