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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
5AGC3
3UCG5
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
3UCG5
ACU
3UCG5
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.
GT  GC + AT
GT  GC + AT
Point mutation, transition
pyrimidinepyrimidine
purinepurine
Point mutation, transversion
GC  CG,
TA  AT,
GC  TA
pyrimidinepurine
purinepyrimidine
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
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