ライフサイエンスコーパス: dGTP

1 dGTP is the best substrate among the deoxyribonucleoside

2 r-binding sites, site 1 binding dGTP, site 2 dGTP or dATP.

3 resumably through chain termination, with 3' dGTP having the highest potency.

4 d as donors, the substrate analog 2'-Mant-3'-dGTP as acceptor.

5 , X = H) and corresponding beta,gamma-CXN(3) dGTP (5-6) and alpha,beta-CXN(3) dATP (7-8) analogues ar

6 Interestingly, the discrimination against a dGTP:T mismatch is 16.5 times lower than that of a dTTP:

7 unopposed by a primer base and followed by a dGTP:A mismatch pair at the active site, representative

8 We show that SAMHD1 contains a dGTP-regulated deoxynucleotide triphosphohydrolase.

9 the addition of 7-deaza-2'-deoxyguanosine, a dGTP analog to the PCR mixture and a novel standardized

10 The Escherichia coli dgt gene encodes a dGTP triphosphohydrolase whose detailed role still remai

11 -1) for a dCTP:C mispair to 1.16 s(-1) for a dGTP:T mispair.

12 SAMHD1 is a dGTP-activated dNTPase that has been implicated as a mod

13 It has been proposed that SAMHD1 is a dGTP-dependent deoxynucleoside triphosphohydrolase (dNTP

14 in- and HD domain-containing protein 1) is a dGTP-dependent dNTP triphosphohydrolase that converts dN

15 atalytically active recombinant dNTPase is a dGTP-induced tetramer.

16 alytic activity and induces disassembly of a dGTP-dependent oligomer.

17 SAMHD1, a dGTP-regulated deoxyribonucleoside triphosphate (dNTP) t

18 ate incoming nucleotides including A:dCTP, A:dGTP, A(syn):dGTP, A:dATP, A(syn):dATP, T:dCTP, and T:dG

19 tions by pol mu: T:dGTP<A(syn):dATP<T:dCTP<A:dGTP<A(syn):dGTP<A:dCTP<A:dATP.

20 cleotide insertions, with the exception of A:dGTP, which may be more sensitive to the template sequen

21 DinB selectively adds dGTP across from tC in template DNA but cannot extend be

22 ffector-pairs bound (CDP/dATP, UDP/dATP, ADP/dGTP, GDP/TTP) that reveal the conformational rearrangem

23 -2'-deoxyguanosine triphosphate (N(2) -alkyl-dGTP) derivatives with methyl, butyl, benzyl, or 4-ethyn

24 D1 mutations and mutations in the allosteric dGTP-binding site of SAMHD1 for defects in RNase or dNTP

25 fluorescent nucleotide analogue, 3'-O-allyl-dGTP-PC-Bodipy-FL-510, as a reversible terminator for SB

26 ocleavable fluorescent nucleotide analogues (dGTP-PC-Bodipy-FL-510, dUTP-PC-R6G, dATP-PC-ROX, and dCT

27 misincorporate dCTP opposite template C and dGTP opposite template G with significantly higher effic

28 We used a series of dATP and dGTP analogues to determine how DNA polymerase I from Ba

29 correlated with the suppression of dATP and dGTP levels caused by stable expression of R2-targeted s

30 (dNTP) values for the insertion of dATP and dGTP opposite 7-deazaadenine and 7-deazaguanine were dec

31 the discrimination by Dpo4 between dATP and dGTP opposite DFT and its inability to extend beyond a G

32 , hpol eta preferred to incorporate dATP and dGTP, compared with dTTP.

33 ubstitutes for natural dTTP, dCTP, dATP, and dGTP in PCR.

34 ration increased 2-fold normal, and dCTP and dGTP concentrations rose less than 1-fold normal.

35 ols, whereas during quiescence, the dCTP and dGTP pools decrease to 50% of the control.

36 t Arg-363 is responsible for dATP, dCTP, and dGTP hydrolysis, whereas Arg-504 and Ser-319 confer dTTP

37 idizes the guanine moiety of dGuo, dGMP, and dGTP to 2-Ih, and both peracetic and m-chloroperbenzoic

38 ion of the monomeric species dGuo, dGMP, and dGTP.

39 hilus PolC in a ternary complex with DNA and dGTP.

40 Our finding of dTTP and dGTP elevations and dATP depletion in mitochondrial dNTP

41 In whole-cell extracts, dTTP and dGTP pools also expanded, but somewhat less than in mito

42 medium, we found the mitochondrial dTTP and dGTP pools to expand significantly, the dCTP pool to dro

43 REV1 misincorporated dTTP and dGTP with much lower frequencies.

44 cluding dGTP/dATP, dGTP/dCTP, dGTP/dTTP, and dGTP/dUTP.

45 TP opposite A (dATP/A) as well as dATP/G and dGTP/G were decreased greater than 10-fold with the deaz

46 Ecm1 also methylates GpppA, GDP, and dGTP but not ATP, CTP, UTP, ITP, or m(7)GTP.

47 shown to interact specifically with GTP and dGTP; no other naturally occurring nucleotides that were

48 hesis of guanosine 5'-triphosphate (GTP) and dGTP and is responsible for the phosphorylation of guano

49 formation upon formation of the tetramer and dGTP effector binding.

50 en the TTD and dATP than between the TTD and dGTP.

51 e analogs or normal deoxynucleotides such as dGTP.

52 r the NTP specificity of RtcB such that ATP, dGTP or ITP is used efficiently.

53 Because dGTP is the endogenous competitor of GCV triphosphate, d

54 N(2) -Benzyl-dGTP was equal to dGTP as a substrate for DNA polymerase

55 tical effector-binding sites, site 1 binding dGTP, site 2 dGTP or dATP.

56 mpetitive relationship between dGDP and both dGTP, dGMP, whereas dTDP appears to have a mixed type of

57 of apo-EF1143 and the protein bound to both dGTP and dATP suggested allosteric regulation of its enz

58 In the BrG.dGTP ternary structure, BrG adopts syn conformation and

59 eric regulation of its enzymatic activity by dGTP binding at four identical allosteric sites.

60 hydrolase activity of SAMHD1 is regulated by dGTP availability in the cell.

61 TPase activity of SAMHD1 can be regulated by dGTP, with which SAMHD1 assembles into catalytically act

62 telomerase activity is modulated in vivo by dGTP levels.

63 gt gene, encoding a previously characterized dGTP triphosphohydrolase.

64 diastereomers: (S)- and (R)-beta,gamma-CHCl-dGTP (12a-1/12a-2) and (S)- and (R)-beta,gamma-CHF-dGTP

65 12a-1/12a-2) and (S)- and (R)-beta,gamma-CHF-dGTP (12b-1/12b-2).

66 solution of the corresponding beta,gamma-CHF-dGTP spectra, stating further that 1 decomposed under th

67 Stereopreference for the (R)-CHF-dGTP diastereomer was abolished for k(pol) but not K(d)

68 thesized the first individual beta,gamma-CHX-dGTP diastereomers [(R)- or (S)-CHX, where X is F or Cl]

69 The Escherichia coli dGTP triphosphohydrolase (dGTPase) encoded by the dgt ge

70 aphic results for a series of beta,gamma-CXY dGTP analogues, where X,Y = H, F, Cl, Br, and/or CH(3).

71 insert the incoming nucleotide, since K(d)((dGTP)) is not affected.

72 to reactive oxygen species, known to damage dGTP and GTP to 8-oxo-dGTP and 8-oxo-GTP, respectively.

73 e opposite to the incoming dNTP (dCTP, dATP, dGTP) is oxoG.

74 ixtures of nucleotides, including dGTP/dATP, dGTP/dCTP, dGTP/dTTP, and dGTP/dUTP.

75 GDP, C site) as well as ATP and dNTPs (dATP, dGTP, TTP) allosteric effectors that control enzyme acti

76 The dATP/dGTP insertion ratio opposite the dGh/dIa site as a func

77 increased more than 4-fold normal, and dCTP, dGTP, and dATP concentrations rose 1-2 times normal.

78 nucleotides, including dGTP/dATP, dGTP/dCTP, dGTP/dTTP, and dGTP/dUTP.

79 ich were eliminated by the addition of deaza-dGTP, consistent with these specific pauses being a cons

80 hate pools showed that hydroxyurea decreased dGTP pools without significantly affecting ganciclovir t

81 ous competitor of GCV triphosphate, depleted dGTP at the time of GCV addition results in increased GC

82 NSAH depresses dGTP and dATP levels in the dNTP pool causing S-phase ar

83 15A mutation disrupted MgdGTP binding and dG:dGTP ternary complex formation but not dG:dCTP ternary c

84 epair polymerase that catalyzes efficient dG:dGTP incorporation in addition to correct repair.

85 l substrate binding and the most frequent dG:dGTP misincorporation of AsfvPolX remain poorly understo

86 hydrophobic residues Val120 and Leu123 in dG:dGTP misincorporation and can provide information for ra

87 ented strategies to achieve the mutagenic dG:dGTP incorporation.

88 dGTP), and ternary (Pol X:DNA:MgdGTP with dG:dGTP non-Watson-Crick pairing) forms, along with functio

89 substrates much less efficiently than it did dGTP.

90 The phosphate donors are dTTP, dGTP, and ribo-GTP as well as the thymidine and guanosin

91 ns are stimulated by the allosteric effector dGTP, and epimerization is not detected in the absence o

92 pyrimidines over purines, whereas effectors dGTP and TTP select for substrates ADP and GDP, respecti

93 g the deoxyguanosine derived from endogenous dGTP degraded by SAMHD1 in the nucleus.

94 eotide reductase, to decrease the endogenous dGTP pool, which should lessen competition with ganciclo

95 ial extracts and found that GTP pools exceed dGTP pools by 50-fold or less, not enough to interfere w

96 merase I from Escherichia coli accepted Fapy.dGTP and beta-C-Fapy.dGTP as substrates much less effici

97 chia coli accepted Fapy.dGTP and beta-C-Fapy.dGTP as substrates much less efficiently than it did dGT

98 ient hydrolysis of Fapy.dGTP and beta-C-Fapy.dGTP by MutT, the E. coli enzyme that releases pyrophosp

99 ) and its C-nucleoside analogue (beta-C-Fapy.dGTP) were synthesized.

100 s enhanced by inefficient hydrolysis of Fapy.dGTP and beta-C-Fapy.dGTP by MutT, the E. coli enzyme th

101 amino-4-hydroxy-5-f ormamidopyrimidine (Fapy.dGTP) and its C-nucleoside analogue (beta-C-Fapy.dGTP) w

102 if 1% of the dGTP pool is converted to Fapy.dGTP.

103 rimination factor of approximately 50 favors dGTP over acyclovir triphosphate, mostly due to a faster

104 ity than dATP, while polymerase alpha favors dGTP over dATP by a factor of 30-65.

105 CHF carbon, as in beta,gamma-fluoromethylene-dGTP, which forms an active site complex with DNA polyme

106 -1)): k(on)app = 7.2 x 10(4) M(-1) s(-1) for dGTP and k(on)app = 2.8 x 10(7) M(-1) s(-1) for 8-oxo-dG

107 te binding: k1 = 1.9 x 10(6) M(-1) s(-1) for dGTP and k1 = 0.75 x 10(9) M(-1) s(-1) for 8-oxo-dGTP (t

108 dimeric and indicates a molecular basis for dGTP stimulation of catalytic activity against dNTPs.

109 h a specific lowering of the apparent Km for dGTP.

110 are 3.5 nM for 8-oxo-dGTP and 62 microM for dGTP, indicating that 8-oxo-dGTP binds 1.8 x 10(4)-fold

111 y range from 1 error in 3563 nucleotides for dGTP:T to 1 error in 2.3 x 10(6) nucleotides for dCTP:C.

112 The preference for dGTP insertion is explained by a 5'-slippage pattern in

113 e context reveal significant selectivity for dGTP insertion that predominantly yields -1 deletion ext

114 pproximately 10,000-fold lower than that for dGTP.

115 The tetramer contains four dGTP specific allosteric regulatory sites and four activ

116 ation ions (e.g., discrimination of ATP from dGTP).

117 The deoxyguanosine released by SAMHD1 from dGTP can be phosphorylated inside mitochondria by deoxyg

118 and dTDP, respectively, by using either GTP, dGTP or dTTP as the phosphate donor.

119 formation of a second-sphere MutT-M2+-(H2O)-dGTP complex, but slows the iso step (k5) 5.8-fold, and

120 However, dGTP pools also declined parallel to the dTTP decrease.

121 sites adjacent to the previously identified dGTP-binding primary regulatory sites.

122 II, diffracting ternary complexes including dGTP were obtained.

123 exed with mixtures of nucleotides, including dGTP/dATP, dGTP/dCTP, dGTP/dTTP, and dGTP/dUTP.

124 s-anti-[BP]-N(2)-dG adduct opposite incoming dGTP, dTTP and dCTP nucleotides, as well as unmodified g

125 rms Hoogsteen base pairing with the incoming dGTP analog.

126 or the A*G and G*G mispair with the incoming dGTP in anti conformation, while the protein remains nea

127 ed G rather than G* is skipped, the incoming dGTP pairs with the C on the 5'-side of G*, and the -1 d

128 Kf(-) polymerase preferentially incorporated dGTP, whereas Taq demonstrated a bias for dATP.

129 I, showed that the Dpo4 polymerase inserted dGTP and dATP when challenged by the PdG adduct.

130 Klenow fragment inserts dGTP with a 4-9-fold higher probability than dATP, while

131 igher doses to achieve greater intracellular dGTP may be beneficial in this patient population.

132 riation in the accumulation of intracellular dGTP without any effect on other deoxynucleotides.

133 orporated per telomerase per minute, with Km(dGTP) approximately 17 muM, indicating super-telomerase

134 ucleotide insertion efficiency (k(cat)/K(m), dGTP-dC) is highly dependent on the sequence identity of

135 Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results

136 eotides such as N6-methyl-dATP and O6-methyl-dGTP are incorporated opposite an abasic site far more e

137 olymerase lambda variant poised to misinsert dGTP opposite a template T.

138 lar, in most tissues examined, mitochondrial dGTP concentrations are high relative to the other dNTPs

139 However, while the mitochondrial dGTP is low in the Mpv17-/- liver, the brain shows no ch

140 7-fold increase in fidelity over the natural dGTP.

141 of polbeta with an incoming nonhydrolyzable dGTP or dCTP analog paired with templating BrG.

142 inopyrazolo[3,4-d]pyrimidin-4-ones are novel dGTP analogues that inhibit the replication-specific enz

143 xo-dGTP needed to reduce fidelity was <1% of dGTP.

144 High accumulation of dGTP in T cells may be dependent on the levels of deoxyn

145 ut as the pH increased to 9.0, the amount of dGTP insertion steadily increased.

146 Analogues of dGTP where the beta-gamma bridging oxygen is replaced wi

147 imics precisely the mutagenic arrangement of dGTP:dT normally preferred by hpol iota.

148 tested under physiological concentrations of dGTP or GTP found in either dividing or non-dividing cel

149 g optimal primers and high concentrations of dGTP, we were able to detect significant type II translo

150 of dTTP results in a concurrent decrease of dGTP due to allosteric regulation of ribonucleotide redu

151 ced on authentic N-RNA with the exception of dGTP, which is incorporated.

152 urnover kinetic studies of the hydrolysis of dGTP and 8-oxo-dGTP and global fitting of the data to th

153 ficiency, while it showed less hydrolysis of dGTP and dTTP.

154 by the dgt gene catalyses the hydrolysis of dGTP to deoxyguanosine and triphosphate.

155 ) and K(m) (<or=4-fold) in the hydrolysis of dGTP, indicating largely intact active sites.

156 ee energy relationships for incorporation of dGTP analogues opposite either template base C or T reve

157 est that the differences in incorporation of dGTP, dCTP, and dTTP are due to the effects of imperfect

158 ficity constant for correct incorporation of dGTP, TTP, and ATP to values of 1.5, 0.35, and 0.044 muM

159 cyclovir to those governing incorporation of dGTP.

160 resulted in accumulation of higher levels of dGTP (40-250 microM) which resulted in increase in apopt

161 Interestingly, the misincorporation of dGTP opposite a template base thymine (0.2 s(-1)) was mo

162 pportunity for increased misincorporation of dGTP.

163 Mispairing of dGTP and dTTP was similar and occurred with k(cat)/K(m)

164 ssay for dNTPs, based upon overestimation of dGTP when GTP levels in extracts are much higher than dG

165 08A-RTPR, and C408S-RTPRs in the presence of dGTP are 5.1, 0.28, and 0.42 s(-1), respectively.

166 h Mg(2+) hydrolysis required the presence of dGTP as an effector, activating the degradation of dATP

167 In addition, we demonstrated the presence of dGTP triphosphohydrolase and nuclease activities in seve

168 C408A-RTPR and C408S-RTPR in the presence of dGTP, the deuterium at the 5'-carbon was stereochemicall

169 rmines the local concentration or quality of dGTP.

170 hate, mostly due to a faster maximum rate of dGTP incorporation.

171 ts on nucleotidyl transfer using a series of dGTP bisphosphonate analogues in which the beta,gamma-br

172 of its Km being 540-fold lower than that of dGTP.

173 In all cases the largest effect was on dGTP, the preferred substrate of SAMHD1.

174 alpha alone with ClFDP or ClFTP, +/- ATP or dGTP, reveals in each case that alpha forms a kineticall

175 s revealed incoming non-hydrolyzable dATP or dGTP analogs not pairing with but instead in a staggered

176 ng Gh from pairing with the incoming dATP or dGTP base.

177 ta with a non-hydrolyzable analog of dATP or dGTP opposite an abasic site, H-bonding was observed bet

178 hexamers, was induced by addition of dATP or dGTP, but not of dTTP or dCTP.

179 deoxyribose nucleotide triphosphate, dATP or dGTP, to Pol eta complexed with undamaged or damaged DNA

180 n edge, which can hydrogen-bond with dATP or dGTP.

181 uld be efficiently replaced by GTP, dATP, or dGTP but not by CTP, UTP, dCTP, or dTTP.

182 ta-DNA complexes and incoming dCTP, dATP, or dGTP opposite 8-oxoG reveal that an arginine from the fi

183 dATP or dTTP incorporation than for dCTP or dGTP into complementary, homopolymeric DNA templates.

184 e composite s-site binds ATP, dATP, dTTP, or dGTP and determines which substrate to reduce.

185 how SAMHD1 is activated by binding of GTP or dGTP at allosteric site 1 and a dNTP of any type at allo

186 of ClFDP from E*ClFDP* by ClFTP (A site) or dGTP (S site) and its inhibition of D57N-alpha together

187 Dpo4 strongly prefers dATP opposite DFT over dGTP (approximately 200-fold) and that the polymerase is

188 TP binding is thermodynamically favored over dGTP binding at both thymine positions of the TTD, most

189 er, the brain shows no change in the overall dGTP pool, leading us to suggest that Mpv17 determines t

190 and k1 = 0.75 x 10(9) M(-1) s(-1) for 8-oxo-dGTP (the latter near the diffusion limit).

191 Pol alpha also polymerized 8-oxo-dGTP across from a templating A, and removing N(6) from

192 Delivery of 8-oxo-dGTP and 2-OH-dATP to zebrafish embryos was highly toxic

193 obtained from k(-1)/k1, are 3.5 nM for 8-oxo-dGTP and 62 microM for dGTP, indicating that 8-oxo-dGTP

194 ecies, known to damage dGTP and GTP to 8-oxo-dGTP and 8-oxo-GTP, respectively.

195 studies of the hydrolysis of dGTP and 8-oxo-dGTP and global fitting of the data to this mechanism ha

196 o the well-characterized hydrolysis of 8-oxo-dGTP at the alpha-beta position, MutT cleaves at the bet

197 nd 62 microM for dGTP, indicating that 8-oxo-dGTP binds 1.8 x 10(4)-fold tighter than dGTP, correspon

198 single-turnover studies with dGTP and 8-oxo-dGTP hydrolysis showed slow apparent second-order rate c

199 ange, we report here the proportion of 8-oxo-dGTP in the dNTP pool that would be needed to reduce the

200 While 8-oxo-dGTP incorporation into DNA is mutagenic, it is not clea

201 e time-lapse crystallography to follow 8-oxo-dGTP insertion opposite adenine or cytosine with human p

202 eover, direct measurements reveal that 8-oxo-dGTP is present at such concentrations in the mitochondr

203 or relatively balanced, the amount of 8-oxo-dGTP needed to reduce fidelity was <1% of dGTP.

204 BF very efficiently polymerized 8-oxo-dGTP opposite adenine, and N1 and N7 of adenine appear t

205 ncorporation of the damaged nucleotide 8-oxo-dGTP opposite to undamaged templates in the context of b

206 scrimination when either incorporating 8-oxo-dGTP or translesion synthesis opposite 8-oxo-dG.

207 ultiple-turnover studies with dGTP and 8-oxo-dGTP show bursts of product formation, indicating partia

208 MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP with a Km of approximately 50 muM and

209 other MutT proteins, MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP, and 8-oxo-GTP to 8-oxo-GDP.

210 to MutT, which hydrolyzes specifically 8-oxo-dGTP to 8-oxo-dGMP.

211 ities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis.

212 a nucleotide sanitizer that hydrolyzes 8-oxo-dGTP to the monophosphate, or that lack MutM and MutY, D

213 and computational analysis reveals how 8-oxo-dGTP uses charge modulation during insertion that can le

214 When 8-oxo-dGTP was added at 0.34 microm to an in vitro DNA replica

215 While correct incorporation of 8-oxo-dGTP was largely unchanged, the level of incorporation o

216 Third, 8-oxo-dGTP was observed to be the best substrate for DR_1025 o

217 here in reactions performed in vitro, 8-oxo-dGTP was readily incorporated opposite template A and th

218 s from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn)

219 For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves re

220 GTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn) uses its Hoogsteen edge to base pair with aden

221 ves 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) and 8-oxo-guanosine triphosphate (8-oxo-GTP) from

222 -7,8-dihydroguanosine-5'-triphosphate (8-oxo-dGTP) show this same phenomena.

223 NA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP).

224 and free energy diagrams indicate that 8-oxo-dGTP, at low concentrations, is a better substrate than

225 reverse transcribed in the presence of 8-oxo-dGTP, dPTP or both, followed by forward transcription in

226 r range) for their natural substrates (8-oxo-dGTP, dUTP, dITP, 2-oxo-dATP), which allows them to sele

227 st substrate for MutT is the mutagenic 8-oxo-dGTP, on the basis of its Km being 540-fold lower than t

228 nucleotide pool of oxidatively damaged 8-oxo-dGTP, preventing mutagenesis by this nucleotide.

229 With 8-oxo-dGTP, the slow steps are the release of the 8-oxo-dGMP p

230 he oxidized deoxyguanosine nucleotide, 8-oxo-dGTP, to its corresponding monophosphate.

231 n of MTH1 expression, which hydrolyzes 8-oxo-dGTP, was accompanied by increased total cellular 8-oxog

232 One such oxidation product is 8-oxo-dGTP, which can compete with dTTP for incorporation oppo

233 ging the mutagenic oxidised nucleotide 8-oxo-dGTP.

234 k(on)app = 2.8 x 10(7) M(-1) s(-1) for 8-oxo-dGTP.

235 ases that process base pairs involving 8-oxo-dGTP.

236 e presence of a two-stage mechanism of 8-oxo-dGTP/8-oxo-GTP detoxification in mycobacteria.

237 ished levels of DNA precursors, particularly dGTP and dATP.

238 both DNA polymerases efficiently polymerize dGTP and dATP when tC and tCo are in the template strand

239 Here we show that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxyn

240 on by removing deoxyguanosine and preventing dGTP imbalance.

241 d template-primer DNA reveal non-productive (dGTP and dATP) alignments of incoming nucleotide and 8-o

242 on of SAMHD1 enzymatic activity and revealed dGTP-induced association of two inactive dimers into an

243 gs are consistent with in vitro data showing dGTP-dependent stimulation of telomerase activity in mul

244 mu: T:dGTP<A(syn):dATP<T:dCTP<A:dGTP<A(syn):dGTP<A:dCTP<A:dATP.

245 nucleotides including A:dCTP, A:dGTP, A(syn):dGTP, A:dATP, A(syn):dATP, T:dCTP, and T:dGTP to study t

246 ing primarily helix alphaE, the prebound syn-dGTP forms a Hoogsteen base pair with the template anti-

247 ld, due to increased formation of template T.dGTP mismatches that are inefficiently corrected by proo

248 yn):dGTP, A:dATP, A(syn):dATP, T:dCTP, and T:dGTP to study the structure-function relationships invol

249 f non-cognate system insertions by pol mu: T:dGTP<A(syn):dATP<T:dCTP<A:dGTP<A(syn):dGTP<A:dCTP<A:dATP

250 Because GTP is 1000-fold more abundant than dGTP in cells, GTP was able to activate the enzyme to a

251 activate the enzyme to a greater extent than dGTP, suggesting that GTP is the primary activator of SA

252 GTP levels in extracts are much higher than dGTP levels.

253 w concentrations, is a better substrate than dGTP because it binds to MutT 395-fold faster, dissociat

254 oxo-dGTP binds 1.8 x 10(4)-fold tighter than dGTP, corresponding to a 5.8 kcal/mol lower free energy

255 mulated by TPP1-POT1 overexpression and that dGTP usage by this variant was less efficient compared w

256 It has previously been established that dGTP acts as both an activator and a substrate of this e

257 ral and enzyme kinetic studies indicate that dGTP binding to the first allosteric site, with nanomola

258 The dGTP accumulation was related to induction of apoptosis

259 The dGTP did not pair with PdG, but instead with the 5'-neig

260 e catalytic complex assembly and enhance the dGTP misincorporation efficiency.

261 D1 and dGK interact in the regulation of the dGTP pool during quiescence employing dGK-mutated skin f

262 el of Fapy.dG observed in cells if 1% of the dGTP pool is converted to Fapy.dGTP.

263 take place, suggests that alterations of the dGTP pools as well as alterations in the level of some m

264 ng and a faster rate of incorporation of the dGTP:T mismatch relative to the dTTP:G mismatch.

265 diasteromers (6/7, 8/9, 10/11) populate the dGTP site in the enzyme complex about equally.

266 sine during the 5-FC incubation reverses the dGTP depletion, reduces the amount of GCV monophosphate

267 ues for the m6dGTP substrate relative to the dGTP substrate was greater for both variant polymerases

268 two lines was considerably greater when the dGTP analogue formed an incorrect (G.T) rather than a co

269 ld or less, not enough to interfere with the dGTP assay.

270 itro and cellular results argued that 6-thio-dGTP and 6-thio-GTP are favored substrates for NUDT15, a

271 effector metabolites 6-thio-deoxyGTP (6-thio-dGTP) and 6-thio-GTP, thereby limiting the efficacy of t

272 N(2) -Benzyl-dGTP was equal to dGTP as a substrate for DNA polymerase kappa (pol kappa)

273 mismatches occur with fidelities similar to dGTP with the exception of the CH2 analogue, which is in

274 dation of 2'-deoxyguanosine-5'-triphosphate (dGTP) from singlet oxygen provide either dSpTP or dGhTP

275 Intracellular deoxyguanosine triphosphate (dGTP) increase was very modest, from median of 6 microM

276 Intracellular deoxyguanosine triphosphate (dGTP) increased by 2- to 40-fold in 4 of 5 patients (8 o

277 t intracellular deoxyguanosine triphosphate (dGTP) levels positively correlate with both telomere len

278 Forodesine-promoted dGuo triphosphate (dGTP) accumulation and GTP and ATP depletion in CLL cell

279 increase in intracellular dGuo triphosphate (dGTP).

280 antly increased the ganciclovir triphosphate:dGTP value for 12 to 24 hours in HSV-TK-expressing and b

281 ged increase in the ganciclovir triphosphate:dGTP value in cells in coculture resulted in synergistic

282 po-, AMPPNP only-, AMPPNP-CDP-, AMPPNP-UDP-, dGTP-ADP- and TTP-GDP-bound complexes give insight into

283 reports indicate that the ratio of undamaged dGTP to dTTP in mitochondrial dNTP pools from rodent tis

284 Here we use dGTP analogues replacing the beta,gamma-bridging O with

285 imination drops to 1,100-fold for GTP versus dGTP.

286 With dGTP as the substrate, replacing Mg2+ with Mn2+ does not

287 With dGTP placed opposite 8-oxoG, pairing was not to the 8-ox

288 With dGTP, the slow steps are the chemical step (k2 = 10.7 s(

289 sue mitochondria are highly asymmetric, with dGTP predominating, and that the imbalance probably cont

290 or substrate for HIV RT and can compete with dGTP for incorporation into DNA.

291 crystal structure of EF1143 in complex with dGTP and dTTP.

292 ray structures of R293A ScRR1 complexed with dGTP and AMPPNP-CDP [AMPPNP, adenosine 5-(beta,gamma-imi

293 vating the degradation of dATP and dCTP with dGTP also being consumed in the reaction with dATP.

294 tives as well as dNMPs were also formed with dGTP, dCTP, or dTTP.

295 ; however, the activity levels observed with dGTP and GTP were 4.7 and 2.5 times the levels observed

296 se is ~3-fold higher than that obtained with dGTP for dGMP kinase (1.3 x 10(-4) M), indicating that a

297 1 by siRNA expands all four dNTP pools, with dGTP undergoing the largest relative increase.

298 iso" mechanism, single-turnover studies with dGTP and 8-oxo-dGTP hydrolysis showed slow apparent seco

299 Multiple-turnover studies with dGTP and 8-oxo-dGTP show bursts of product formation, in

300 r rate is higher for one mismatch (e.g., T x dGTP) than for its complement (A x dCTP).