ライフサイエンスコーパス: dGTP

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

21 -2'-deoxyguanosine triphosphate (N(2) -alkyl-dGTP) derivatives with methyl, butyl, benzyl, or 4-ethyn

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

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

24 not be turned off by combinations of ATP and dGTP/dTTP.

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

26 hat hpol eta favors the addition of dATP and dGTP opposite 1,N (6)-erA.

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

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

29 s indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N (6)-erA.

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

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

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

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

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

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

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

37 REV1 misincorporated dTTP and dGTP with much lower frequencies.

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

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

40 al studies, we demonstrate that both GTP and dGTP bind to Rel, but only GTP (but not dGTP) can form t

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

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

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

44 serting with similar catalytic efficiency as dGTP.

45 e analogs or normal deoxynucleotides such as dGTP.

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

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

48 However, the mechanism behind dGTP selectivity is unclear.

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

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

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

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

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

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

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

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

57 telomerase activity is modulated in vivo by dGTP levels.

58 gt gene, encoding a previously characterized dGTP triphosphohydrolase.

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

60 12a-1/12a-2) and (S)- and (R)-beta,gamma-CHF-dGTP (12b-1/12b-2).

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

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

63 sly reported the (R)- and (S)-beta,gamma-CHX-dGTP diastereomers (X = F, Cl), prepared via P,C-dimorph

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

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

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

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

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

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

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

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

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

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

74 hate (3TC-TP)/ETV-triphosphate (ETV-TP)/dCTP/dGTP.

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

76 ctivation in heart led to strongly decreased dGTP and increased dCTP, dTTP, and dATP pools; aberrant

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

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

79 15A mutation disrupted MgdGTP binding and dG:dGTP ternary complex formation but not dG:dCTP ternary c

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

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

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

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

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

85 substrates much less efficiently than it did dGTP.

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

87 ctural studies of polbeta incorporating dTTP/dGTP opposite oxoA.

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

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

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

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

92 ic data indicate that binding of beta-C-Fapy*dGTP impedes enzyme closure, thus hindering insertion.

93 site residue, Asp276, positions beta-C-Fapy*dGTP so that it distorts the geometry of critical cataly

94 ionally stable Fapy*dGTP analog, beta-C-Fapy*dGTP, with DNA polymerase beta.

95 ore, under oxidative stress conditions, Fapy*dGTP could become a pro-mutagenic substrate for insertio

96 is in its nucleotide triphosphate form, Fapy*dGTP, it is inefficiently cleansed from the nucleotide p

97 A polymerase beta has evolved to hinder Fapy*dGTP insertion.

98 tructures of a configurationally stable Fapy*dGTP analog, beta-C-Fapy*dGTP, with DNA polymerase beta.

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

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

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

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

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

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

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

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

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

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

109 -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

110 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

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

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

113 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

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

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

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

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

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

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

120 e active site does not discriminate GTP from dGTP, for a substrate.

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

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

123 unexpectedly asymmetric, with unusually high dGTP and GTP levels compared with those in whole mouse e

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

125 ly known enzyme that specifically hydrolyzes dGTP.

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

127 II, diffracting ternary complexes including dGTP were obtained.

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

129 rms Hoogsteen base pairing with the incoming dGTP analog.

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

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

132 oleta readily bypassed oxoA, it incorporated dGTP opposite oxoA with a catalytic specificity comparab

133 Poleta and polbeta incorporated dGTP opposite oxoA ~170-fold and ~100-fold more efficien

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

135 erase eta (poleta) proficiently incorporates dGTP opposite oxoA, suggesting the nascent oxoA:dGTP ove

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

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

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

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

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

141 Here we present the free-, ligand (dGTP)- and inhibitor (GTP)-bound structures of hexameric

142 s, with the exception of a Watson-Crick-like dGTP insertion opposite T, using BER DNA ligases in vitr

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

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

145 t MTH1 is an efficient catalyst of O6-methyl-dGTP hydrolysis suggesting that MTH1 may also sanitize t

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

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

148 7-fold increase in fidelity over the natural dGTP.

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

150 and dGTP bind to Rel, but only GTP (but not dGTP) can form the product.

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

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

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

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

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

156 ns, and the dGp5dC dimer as a combination of dGTP and dCTP.

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

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

159 In contrast, the catalytic efficiency of dGTP insertion decreases ~20-fold when 5-carboxycytosine

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

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

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

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

164 atalytic efficiency for the incorporation of dGTP catalyzed by human DNA polymerase beta is not affec

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

166 cyclovir to those governing incorporation of dGTP.

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

168 pportunity for increased misincorporation of dGTP.

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

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

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

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

173 rmines the local concentration or quality of dGTP.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

199 Second, free 8-oxo-dGTP can be misincorporated by DNA polymerases into DNA

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

221 -7,8-dihydroguanosine-5'-triphosphate (8-oxo-dGTP) show this same phenomena.

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

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

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

225 eobase whose deoxyribonucleotide form, 8-oxo-dGTP, has been widely studied and demonstrated to be a m

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

227 hic analyses revealed that, similar to 8-oxo-dGTP, r8-oxo-GTP adopts an anti conformation opposite a

228 However, unlike 8-oxo-dGTP, r8-oxo-GTP did not form a planar base pair with ei

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

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

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

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

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

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

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

236 sertion efficiency ~55-fold, indicating oxoA:dGTP misincorporation was promoted by minor groove inter

237 P opposite oxoA, suggesting the nascent oxoA:dGTP overcomes the geometric discrimination of poleta.

238 Also, the efficiency of oxoA:dGTP insertion by the X-family polbeta decreased ~380-fo

239 Gln38-mediated minor groove contacts to oxoA:dGTP.

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

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

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

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

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

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

246 ormational changes are coupled to substrate (dGTP), but not inhibitor binding, since GTP locks dGTPas

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

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

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

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

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

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

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

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

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

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

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

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

259 The dGTP accumulation was related to induction of apoptosis

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

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

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

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

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

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

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

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

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

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

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

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

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

273 ing oxidized 2-OH-dATP or therapeutic 6-thio-dGTP, but insertion disrupts translocation and inhibits

274 hat telomerase poorly selects against 6-thio-dGTP, inserting with similar catalytic efficiency as dGT

275 when Asn279-mediated minor groove contact to dGTP was abolished.

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

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

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

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

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

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

282 increase in intracellular dGuo triphosphate (dGTP).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

297 When paired with dGTP, oxoA adopted a syn conformation and formed a Hoogs

298 When paired with dGTP, oxoA adopted a syn-conformation and formed Hoogste

299 1 by siRNA expands all four dNTP pools, with dGTP undergoing the largest relative increase.

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

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