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1 dTTP is the most abundant deoxynucleoside triphosphate (
2 dTTP misinsertion frequency opposite template G was incr
3 he short-range beta-particles emitted by [3H]dTTP result in self-irradiation of labeled CHO cells; th
4 Treatment of CHO cells with 100 microCi [3H]dTTP resulted in a 14-fold increase in bystander mutatio
5 s were labeled with tritiated thymidine ([3H]dTTP) for 12 hours and subsequently incubated with A(L)
6 T7 helicase hydrolyzes dTTP at a rate of 49 dTTP per second per hexamer, which indicates that the en
8 we present the first crystal structure of a dTTP-bound deoxycytidylate deaminase from the bacterioph
9 mismatch is 16.5 times lower than that of a dTTP:G mismatch due to a tighter Kd for ground state bin
10 l pathway; while a pol mu complex with the A:dTTP base pair is available, no solved non-cognate struc
11 ge pathway based on the presence of adequate dTTP pools, normal thymidylate synthase (TS) activity, p
12 g-493 and Asn-468 are replaced with alanine, dTTP hydrolysis is no longer stimulated in the presence
15 the acrolein and crotonaldehyde adducts, and dTTP incorporation was preferred at the butadiene- and s
16 hat T7 helicase binds and hydrolyses ATP and dTTP by competitive kinetics such that the unwinding rat
17 more, the simulations indicate that dATP and dTTP are better incorporated in the damaged system than
22 the results indicate that elevated dCTP and dTTP pools increase mismatch formation and decrease erro
23 iota with N(2),3-epsilonG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms.
25 pposite the O(6)-alkylG adducts for dCTP and dTTP with pol eta and kappa; pol iota showed a strong pr
26 ferences in incorporation of dGTP, dCTP, and dTTP are due to the effects of imperfect geometric compl
27 the four nucleotides (dGTP, dATP, dCTP, and dTTP), and the drug-apo riboflavin-binding protein, we s
28 ificity: dissociation constants for dGTP and dTTP are nearly equivalent and K(m) and k(cat) values fo
30 e triphosphate allosteric effectors dGTP and dTTP, and the dimeric murine R2 subunit on both the quat
33 s 2-3-fold expansions of the dATP, dGTP, and dTTP pools, whereas dCTP declines by a comparable amount
34 DNA polymerase with primer-template DNA and dTTP, capturing the step just before primer extension.
37 peripheral blood mononuclear cells; dTMP and dTTP depletion were induced by single exposures to a low
39 iptase discriminates poorly between dUTP and dTTP, and accordingly, viral DNA products become heavily
41 hest activity on dCTP, followed by dUTP, and dTTP inhibits both the deaminase and pyrophosphatase act
43 > REV1 > pol eta approximately pol iota, and dTTP misincorporation is the major miscoding event by al
51 mechanistic implications of the variable bp/dTTP that indicates T7 helicase either undergoes backwar
58 hways are essential for maintaining cellular dTTP pools to ensure the faithful replication of both mi
59 to the noncognate dCTP, neither the cognate dTTP nor its nonhydrolyzable analog induced fingers clos
65 hereas the composite s-site binds ATP, dATP, dTTP, or dGTP and determines which substrate to reduce.
66 sphate pools, particularly an increased dATP:dTTP ratio, which subsequently results in enhanced DNA f
69 ochemically, the intracellular ratio of dATP:dTTP increased substantially in JH-1 cells as cells prog
71 und structures show that both the O6MeG.dCTP/dTTP-Mg(2+) complexes adopt an open protein conformation
73 case domain is responsible for DNA-dependent dTTP hydrolysis, translocation, and DNA unwinding wherea
74 in is not only responsible for DNA-dependent dTTP hydrolysis, translocation, and DNA unwinding, but i
76 O]P(i) exchange experiments failed to detect dTTP synthesis, indicating that the less than six-site h
78 ermediate' protein conformation while the dG*dTTP-Mg2+ complex adopts an open protein conformation.
79 to the dA*dCTP-Mg2+ complex, whereas the dG*dTTP-Mn2+ complex undergoes a large-scale conformational
80 stal structures of polbeta complexed with dG*dTTP and dA*dCTP mismatches in the presence of Mg2+ or M
82 strate analog and specificity effector (dGDP/dTTP or GMP/dTTP) with R1 regulates the redox properties
84 -[BP]-N(2)-dG adduct opposite incoming dGTP, dTTP and dCTP nucleotides, as well as unmodified guanine
86 pletion of TbTK leads to strongly diminished dTTP pools and DNA damage indicating intracellular dThd
88 ed a model system in which the cellular dUTP:dTTP ratio can be pharmacologically increased to favor d
90 xamers predominate in the presence of either dTTP or beta,gamma-methylene dTTP whereas the ratio betw
96 rder of binding affinity was shown to follow dTTP > GTP > ATP > CTP, with differences in binding ener
98 ults indicate that Mg2+ is not necessary for dTTP binding, but Mg2+ is required for optimal hydrolysi
102 postulated to be conformational switches for dTTP-dependent helicase activity leads to modulation of
104 WT pol gamma could discriminate Ed4T-TP from dTTP 12,000-fold better than RT, with only an 8.3-fold d
108 relaxed active-site specificity toward the G-dTTP mispair may be associated with its cellular functio
110 g and specificity effector (dGDP/dTTP or GMP/dTTP) with R1 regulates the redox properties of the diir
115 locating along ssDNA, T7 helicase hydrolyzes dTTP at a rate of 49 dTTP per second per hexamer, which
116 serve that each wild-type subunit hydrolyzes dTTP independently in the absence of single-stranded DNA
117 strongly support TbTK as a crucial enzyme in dTTP homeostasis and identify structural differences wit
118 Further the functional group on C4 (O in dTTP and NH2 in dCTP) makes interactions with nonconserv
119 res of Pol iota with template A and incoming dTTP and with template G and incoming dCTP have revealed
121 5F pol with a correctly base-paired incoming dTTP reveals that the phenylalanine ring is accommodated
122 e interaction with the 3'-OH of the incoming dTTP and that V148I disrupts positioning of Q151 for thi
123 form novel hydrogen bonds with the incoming dTTP and with the enzyme that differ from those formed w
124 re observed between: (i) dF and the incoming dTTP, (ii) dF and residue G568 of the polymerase, and (i
127 Exogenous addition of D-thymidine increased dTTP levels to that in differentiated macrophages but di
128 mechanisms of DNA-dependent and -independent dTTP hydrolysis by the gene 4 protein of bacteriophage T
129 ormation and, consequently, in intracellular dTTP pools, followed by slower recovery in both indices
130 ibits significantly higher Km(dTTP) and Kcat(dTTP) values, implying that the incorporation reaction i
132 253M enzyme exhibits significantly higher Km(dTTP) and Kcat(dTTP) values, implying that the incorpora
133 ordered, in accordance with a much higher Km,dTTP that drives the difference in efficiency between C
135 n incorporated after the analog), 4'C-methyl dTTP causes a pause in DNA synthesis at the point of inc
136 sence of either dTTP or beta,gamma-methylene dTTP whereas the ratio between hexamers and heptamers is
137 DNA in the presence of beta,gamma-methylene dTTP, the primase can function at recognition sites on t
138 In the presence of beta, gamma-methylene dTTP, the protein forms a hexamer that surrounds and bin
139 r in the presence of both Mg-dTMP-PCP and Mg-dTTP are similar, indicating that Mg-dTTP binding is suf
140 and Mg-dTTP are similar, indicating that Mg-dTTP binding is sufficient and hydrolysis is not necessa
142 ion was only one-tenth of that found with Mg.dTTP, as determined by rapid chemical quench assays.
143 lished that both polymerases misincorporated dTTP with high frequency across from cisplatin- and oxal
145 rases, is uniquely prone to misincorporating dTTP opposite template G in a highly sequence-dependent
146 plemented medium, we found the mitochondrial dTTP and dGTP pools to expand significantly, the dCTP po
148 ate analysis indicates that neither dCTP nor dTTP insertion is strongly preferred during polymerizati
150 aza-dATP in place of the natural nucleotides dTTP and dATP, we have demonstrated the simultaneous inc
151 the similar altered conformation, the O6MeG.dTTP-Mn(2+) complex adopts a catalytically competent sta
154 conformational change rates for addition of dTTP opposite 2-AP following the 8-oxoGua base pairs was
155 found that the pre-steady-state addition of dTTP opposite A following all three base pairs by bacter
156 dCTP and may result in a higher affinity of dTTP to the allosteric site conferring its inhibitory ac
158 A sterically undemanding azide analogue of dTTP (AHP dUTP) with an alkyl chain and ethynyl attachme
161 ytidine would facilitate hydrogen bonding of dTTP but not dCTP and may result in a higher affinity of
166 e ring-shaped T7 helicase uses the energy of dTTP hydrolysis to perform the mechanical work of transl
168 alysis of the steps required for fixation of dTTP misinsertion during translesion synthesis past cisp
170 DNA binding stimulates the hydrolysis of dTTP but the mechanism for this two-step control is not
171 We propose that sequential hydrolysis of dTTP is coupled to the transfer of single-stranded DNA f
173 e-stranded DNA and couples the hydrolysis of dTTP to unidirectional translocation and the unwinding o
175 serine 319 reduces the rate of hydrolysis of dTTP without affecting the rate of dATP hydrolysis.
176 winding of duplex DNA with the hydrolysis of dTTP, and catalyze the synthesis of short RNA oligoribon
183 emental effect between the incorporations of dTTP and its thio analogue S(p)-dTTPalphaS, the incorpor
184 s were 2, 75, and 22 microM for insertion of dTTP following Gua.C, 8-oxoGua.C, and 8-oxoGua.A base pa
186 TP binding experiments showed that the Kd of dTTP was unaffected, but the stoichiometry of dTTP bindi
189 mine in more detail the kinetic mechanism of dTTP hydrolysis by a preassembled T7 helicase hexamer in
190 a slight increase in the misincorporation of dTTP across from the 3'-G was found for oxaliplatin comp
192 eported earlier, and they support a model of dTTP hydrolysis by T7 helicase hexamer that is similar t
193 the positioning of the nucleoside moiety of dTTP is almost identical to that previously described fo
195 lost H-bonding interaction with the 3'-OH of dTTP, showed higher but similar K(d) values for dTTP, dd
200 deficiency in the intramitochondrial pool of dTTP relative to dCTP in cells from patients with TK2 de
202 Gel filtration of 4A' in the presence of dTTP without Mg2+ showed that Mg2+ was not necessary, an
206 nce assay, and it was found that the rate of dTTP hydrolysis on the helicase active site is eight tim
208 ggest that the CD/5-FC-mediated reduction of dTTP results in a concurrent decrease of dGTP due to all
209 in factor in the preferential selectivity of dTTP opposite O(6)-methylG by human pol iota, in contras
214 cates that the energy from hydrolysis of one dTTP drives unidirectional movement of T7 helicase along
218 of the T7 helicase domain with bound dATP or dTTP identified Arg-363 and Arg-504 as potential determi
219 a nearly 2-fold longer duration for dATP or dTTP incorporation than for dCTP or dGTP into complement
220 ofluorene lesion and can incorporate dCTP or dTTP across from this lesion, suggesting that the bypass
221 ructures of polbeta with an incoming dCTP or dTTP analogue base-paired with O6MeG in the presence of
224 lG as the template base and incoming dCTP or dTTP were solved and showed that O(6)-methylG is rotated
228 duced incorporation of exogenous alpha (32)P-dTTP in fibroblasts from a patient with Alpers syndrome
230 kes cells unable to synthesize DNA precursor dTTP, with the nature of chromosomal damage still unclea
231 operties of the nucleotides (fully replacing dTTP) with TAQ polymerase during PCR have been investiga
232 hough radiosensitization with FdUrd requires dTTP depletion and S-phase arrest, the exact mechanism b
235 was added to a ternary complex containing Rh.dTTP opposite dAP, the templating base, nucleotidyl tran
236 occupancy on the affinity of an incoming Rh.dTTP for the RB69 pol-P/T binary complex and on the rate
237 the A site, the affinity of the incoming Rh.dTTP for the RB69 pol-P/T binary complex and the conform
238 ve also demonstrated that the affinity of Rh.dTTP for occupancy of the B metal ion site is dependent
239 ng Ca(2+) concentration in the absence of Rh.dTTP gives only partial quenching of dAP fluorescence.
242 rhodium(III) deoxythymidine triphosphate (Rh.dTTP) to investigate the requirements of metal binding t
247 Presteady state kinetics of DNA-stimulated dTTP hydrolysis activity of T7 helicase were measured us
251 rmation in the pol iota active site and that dTTP misincorporation by pol iota is the result of Hoogs
252 sing full-length pol iota, which showed that dTTP incorporation occurs with high efficiency opposite
257 tide reductase and severe limitations of the dTTP pools, resulting in thymineless death, the phenomen
260 ence quenching depend hyperbolically on the [dTTP] when a dideoxy-primer/template (ddP/T) with 2AP as
261 uring polymerization with 6-Cl-2APTP, 2-thio-dTTP, or 2-thio-dCTP, the nanocircuit uncovered an alter
262 ded DNA, the subunits of the ring go through dTTP hydrolysis cycles one at a time, and this probably
265 RT would have decreased binding affinity to dTTP analogues lacking 3'-OH, compared to dTTP, the Q151
266 to dTTP analogues lacking 3'-OH, compared to dTTP, the Q151N and V148I RT mutants should have decreas
272 indicate that the ratio of undamaged dGTP to dTTP in mitochondrial dNTP pools from rodent tissues var
274 tion is a sharp rise in the ratio of dUTP to dTTP and subsequent incorporation of dUTP into DNA.
276 ration of 2'-deoxythymidine 5'-triphosphate (dTTP) and 3'-azido-3'-deoxythymidine 5'-triphosphate (AZ
277 mation and a deoxythymidine 5'-triphosphate (dTTP), and that the fit is better for a normal Watson-Cr
280 meric helicase that has been observed to use dTTP, but not ATP, to unwind double-stranded (ds)DNA as
282 T7 DNA helicase preferentially utilizes dTTP to unwind duplex DNA in vitro but also hydrolyzes o
284 nds and hydrolyzes several NTPs, among which dTTP supports optimal protein assembly, DNA binding and
287 binding change mechanism of F(1)-ATPase with dTTP hydrolysis occurring sequentially at the catalytic
288 s discriminated by 77,000-fold compared with dTTP, the discrimination drops to 1,100-fold for GTP ver
290 roduct is 8-oxo-dGTP, which can compete with dTTP for incorporation opposite template adenine to yiel
291 ructure of the HIV-1 RT ternary complex with dTTP proposes that Q151N loses the interaction with the
294 he Q151 residue in HIV-1 RT interaction with dTTP and its analogues containing chemical modifications
296 The K(m) of 4.4 x 10(-4) M obtained with dTTP for dTMP kinase is ~3-fold higher than that obtaine
297 at A257T gp4 is normal in forming rings with dTTP, but the rings do not assemble efficiently on the D
298 assemble on the unwinding DNA substrate with dTTP without Mg(II), and its DNA unwinding activity in e
300 generally support faster DNA unwinding, with dTTP supporting faster rates than any other canonical (d
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