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E. coli CAP +cAMP + DNA HTH motif cAMP ATATAA = consensus sequence of TATA box start point at: Py2CA Py5 TFIID Human TBP complexed at TATA box of DNA 3 ' A T A T A C G T A T 5 'G C octamer CAAT GC TATA start point DNA binding motif of steroid receptors Zn fingers Other DNA binding motifs Helix-turn-helix Helix-loop-helix Additional motif often present in transcription factors Leucine zippers The zinc finger motif is: -Cys-X2-4-Cys-X3-Phe-X5-Leu-X2-His-X3-His- N-terminal C-terminal Zn finger fragment bound to DNA Hormone binding and dimerization regions vary from 5-15% GLUCOCORTICOID RECEPTOR FRAGMENT BOUND TO DNA DNA binding finger N-terminal C-terminal dimerization 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 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 ATT 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 insertion deletion Bacterial nonsense suppressors LOCUS tRNA WILD-TYPE SUPPRESSOR codon/anticodon anticodon/codon supD(su1) Ser UCG CGA CUA UAG supE(su2) Gln CAG CUG CUA UAG supF(su3) Tyr UAUC GUA CUA UAG supC(su4) Tyr AAUC GUA UUA UAAG supG(su5) Lys AAGA UUU UUA UAAG supU(su7) Trp UGG CCA UCA UGAG G O CH3 HN O O HN O CH3 O O O O P O O O O thymine-thymine dimer T T