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Human TBP complexed at TATA box of DNA octamer CAAT GC TATA start point Steroid receptors are the best defined class of transcription factors containing Zn fingers DNA binding motifs: Zn fingers Helix-turn-helix Helix-loop-helix Leucine zippers The zinc finger motif is: -Cys-X2-4-Cys-X3-Phe-X5-Leu-X2-His-X3-His- Zn finger fragment bound to DNA Wobble allows a U•G pairing codon anticodon 1 2 3 O 5AGC3 3UCG5 N N H 3 2 1 O O H AGC N N H2N N N . G U GCU 1 2 3 U in position 1 of the anticodon pairs with A or G in position 3 of codon C G only A U only G C or U AGC 3UCG5 ACU 3UCG5 Cys-X2-Cys-X13-Cys-X2-Cys- C-terminus glucocorticoid specificity GRE recognition finger N-terminus finger Cys 495 Cys 482 Cys 492 Cys 476 dimerization domain homeodomain #2 #1 #3 #1, N-terminal Helix-turn-helix binding motif #3, C-terminal bHLH DNA binding motif of transcription factor MyoD helix 2 helix 1 basic region binding DNA CREB-DNA complex leu selected in zipper domain arg selected in DNA-binding domain Human protooncogenes c-Jun:c-Fos heterodimer Chains: blue = c-Fos, green = c-Jun Residues: red = Leu, purple = Arg 5' 3' G U yeast tRNAphe O Keto-enol tautomerization of Gua N HN O O H2NHN N NN HN N H2N N H2N N N N O H OH O NH OH N N N O N OH N N N keto form H N N HN N NN N N 2 (normal) H2N N N H2N N H2N N N HN N HN N 2 N enol form N 2 H3C O OH N N N O N OH H N HN H HN N O OH N H N ON H pairing properties of enol ON N NN O HN H HN N N N N One round of replication on mismatched strands “fixes the mutation. GT GC + AT GT GC + AT Point mutation, transition pyrimidinepyrimidine purinepurine Point mutation, transversion GC CG, TA AT, GC TA pyrimidinepurine purinepyrimidine nonsense mutation occurs when a termination codon is generated missense mutation occurs when a different amino acid is coded Change of reading frame following the location of a deletion ATA GCA ACC GGC CTT ACA AAT TC ATA GCA ACC GCC TTA CAA AT T C Mechanism for frameshift mutations G-p 3'-G-p-G-p-G-p-G-p-G-p-G-5' 5'-C-p-C p-C-OH 3'-G-p-G-p G-p-G-p-G-p-G-5' 5'-C-p-C-p-C-OH p-C +1 insertion -1 deletion Bacterial nonsense suppressors LOCUS tRNA WILD-TYPE SUPPRESSOR anticodon /codon anticodon/codon supD(su1) Ser CGA UCG CUA UAG supE(su2) Gln CUG CAG CUA UAG sup(su3) Tyr GUA UA UC CUA UAG supC(su4) Tyr GUA AA CU UUA UA GA G supD(su5) Lys UUU AA AG UUA UA GA supD(su7) Trp CCA UGG UCA UG AG O CH3 HN O O CH3 HN N O O O O O N P O O O O T T thymine-thymine dimer F p te