ライフサイエンスコーパス: dTMP

1 dTMP incorporation by DNA pol-gamma was inhibited compet

2 essentially non-mutagenic, whereas about 20% dTMP was inserted opposite the 5'-T of the Dewar photopr

3 y equal to 3'-dCMP approximately equal to 3'-dTMP.

4 nge following the trend 5'dCMP > 5'-dAMP > 5'dTMP >> 5'-dGMP and 3'-dGMP > 3'-dAMP approximately equa

5 For 5'-dCMP- and 5'-dTMP-, a comparison of aqueous ionization energies with

6 For 5'-dCMP- and 5'-dTMP-, the increased favorableness of base ionization, w

7 phosphodiesterase substrate p-nitrophenyl 5'-dTMP (p-Nph-5'-TMP).

8 ergies of 2'-deoxythymidine 5'-phosphate (5'-dTMP-) and 2'-deoxycytidine 5'-phosphate (5'-dCMP-).

9 Although dTMP was inserted efficiently opposite all dA adducts, f

10 of the lesion; misincorporation of dAMP and dTMP also was observed.

11 , accompanied by a small amounts of dAMP and dTMP incorporation and one- and two-base deletions.

12 to a lesser extent, misinsertion of dAMP and dTMP opposite N(4)-CMdC.

13 en C, A, or T was 5' to the lesion; dAMP and dTMP were misincorporated at a frequency of 2-4%.

14 poration of small amounts of dCMP, dAMP, and dTMP opposite the lesion.

15 C, accompanied by lesser amounts of dCMP and dTMP incorporation and base deletion.

16 dCMP and dTMP were most frequently inserted by hPol iota, and onl

17 erved, along with lesser amounts of dGMP and dTMP incorporations and deletions.

18 .7 catalyses the phosphorylation of dGMP and dTMP to dGDP and dTDP, respectively, by using either GTP

19 s (< or =-12 kcal mol-1) for dCMP, dGMP, and dTMP and the least negative value for dAMP.

20 easured for the insertion of dCMP, dGMP, and dTMP opposite the abasic site using single-turnover cond

21 e four mononucleotides dAMP, dCMP, dGMP, and dTMP was studied experimentally by equilibrium measureme

22 he charge-carrying group for dCMP, dGMP, and dTMP.

23 tive domain of TbTK in complex with dThd and dTMP at resolutions up to 2.2 A.

24 intermediate is common to both HETM-dUMP and dTMP formation.

25 Elevated dGMP.G and dTMP.G misincorporation efficiencies of 3.2 x 10(-5) and

26 of formate incorporation into methionine and dTMP was decreased by 90% and 50%, respectively, whereas

27 ncreasing 5,10-methylenetetrahydrofolate and dTMP, enhancing DNA synthesis and thus opposing MTX.

28 tion states for the synthesis of purines and dTMP.

29 was crystallized in the presence of SAM and dTMP and the other with the protein complexed to S-adeno

30 diating the flux of one-carbon units between dTMP and SAM syntheses.

31 dduct in both sequence contexts, followed by dTMP and dGMP.

32 ese structures are also uniquely occupied by dTMP and dCMP resolving aspects of substrate specificity

33 imulated peripheral blood mononuclear cells; dTMP and dTTP depletion were induced by single exposures

34 osphate kinase, gp1.7 exponentially converts dTMP to dTTP.

35 , and to direct the incorporation of correct dTMP opposite this adduct.

36 DE-dG adducts, and incorporated the correct dTMP as well as the incorrect dAMP opposite the DE-dA ad

37 On templates containing dG-AF, dAMP, dTMP, and dCMP were incorporated opposite the lesion in

38 In contrast, dCMP+dTMP+THU therapy decreased life span of Tk2(-/-) animals

39 fe span of Tk2(-/-) animals compared to dCMP+dTMP.

40 ue to a combination of loss of THF-dependent dTMP production by the ThyA enzyme and increased demand

41 cytidine deaminase, leading to elevated dUMP/dTMP ratios.

42 Folate deficiency leads to increased dUMP/dTMP ratios and uracil misincorporation into DNA, which

43 rough a column of immobilized enzyme (either dTMP synthase or dCMP deaminase), and the specifically b

44 n of deoxycytidine deamination might enhance dTMP+dCMP therapy.

45 A primer blocked by 4'C-ethyl dTMP is not extended by HIV-1 RT, and this compound acts

46 ily polymerase, polkappa, was able to extend dTMP inserted opposite a BaP DE dA adduct.

47 K(m) of 70 microM and Kcat of 4.3 s(-1) for dTMP are similar to those found for E. coli thymidylate

48 (m) of 4.4 x 10(-4) M obtained with dTTP for dTMP kinase is ~3-fold higher than that obtained with dG

49 e key enzymes providing one-carbon units for dTMP biosynthesis in the form of 5,10-methylenetetrahydr

50 es the reductive methylation of dUMP to form dTMP and is essential for DNA replication during cell gr

51 ith hydride transfer from H(4)folate to form dTMP.

52 om methylenetetrahydrofolate to dUMP to form dTMP.

53 5),N(10)-methyhlenetetrahydrofolate, forming dTMP for the maintenance of DNA replication and repair.

54 transfer reaction for formation of dTDP from dTMP is a new strategy for anticancer treatment.

55 tD contribute to protect L. pneumophila from dTMP starvation during its intracellular life cycle.

56 ld higher misincorporation rates for dGMP.G, dTMP.G, and dAMP.G mispairs.

57 metabolic switch that, when activated, gives dTMP synthesis higher metabolic priority than SAM synthe

58 sites follows the order dAMP > dGMP > dCMP > dTMP.

59 dNMP decreases in the order of dAMP > dGMP > dTMP > dCMP, from a high of 5.8 when dAMP is to be inser

60 orporation followed the order: dAMP > dGMP > dTMP > dCMP, which did not correlate with the mutational

61 -AAF followed the order dCMP > dAMP > dGMP > dTMP; the frequency of dNTP insertion opposite the lesio

62 dNK(+/-)TK2(-/-) mouse model illustrates how dTMP synthesized in the cell nucleus can compensate for

63 kinetically competent as an intermediate in dTMP formation.

64 ad to inhibition of the enzyme, resulting in dTMP deficiency and cell death.

65 ed dA in vivo by predominantly incorporating dTMP opposite the damaged base.

66 With pol alpha, eta and kappa, incorrect dTMP was preferentially incorporated opposite the lesion

67 talled by the adduct, resulting in increased dTMP incorporation.

68 the ability of bypass polymerases to insert dTMP, dAMP, or dGMP opposite 1,N(6)-gamma-HMHP-dA and de

69 pol beta preferentially inserts dTMP rather than dCMP opposite m6dG.

70 an compensate for loss of intramitochondrial dTMP synthesis in differentiated tissue.

71 es (K(d) = 5 x 10(-6) M, dTTP; 6 x 10(-7) M, dTMP-PCP; 4 x 10(-6) M, dTDP; 3 x 10(-5) M, ATP; 2 x 10(

72 lly extend the primer blocked by the 4' C-Me dTMP analog.

73 idine 5'-(beta, gamma-methylenetriphosphate)(dTMP-PCP), thymidine 5'-diphosphate (dTDP), adenosine 5'

74 med gp4A' hexamer in the presence of both Mg-dTMP-PCP and Mg-dTTP are similar, indicating that Mg-dTT

75 th extremely high fidelity, misincorporating dTMP, dAMP, and dGMP opposite a template G target with e

76 The deoxythymidine monophosphate (dTMP) substrate binding pocket was targeted in a rationa

77 ate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs the life span of Tk2-deficient (Tk2(-/-)

78 e (AdoMet) and deoxythymidine monophosphate (dTMP), which are required for methylation reactions and

79 dine (dThd) forming thymidine monophosphate (dTMP).

80 iosynthesis of deoxythymidine monophosphate, dTMP, required for DNA replication.

81 With all mutants, dTMP formation occurs from occupied forms of both subuni

82 an G, and 5-fold more efficient than natural dTMP misincorporation in adduct bypass.

83 misinsertion of purine nucleotides (but not dTMP) opposite the adducted guanine was observed.

84 amin B12 depletion, which suppresses de novo dTMP biosynthesis and causes DNA damage, accounting for

85 e 5,10-methylenetetrahydrofolate for de novo dTMP biosynthesis and translocate to the nucleus during

86 ovide evidence that impaired nuclear de novo dTMP biosynthesis can lead to both megaloblastic anemia

87 Vitamin B12 depletion decreased de novo dTMP biosynthesis capacity by 5-35%, whereas de novo pur

88 As2O3 inhibited de novo dTMP biosynthesis in a dose-dependent manner, increased

89 of vitamin B12 depletion on nuclear de novo dTMP biosynthesis was investigated in methionine synthas

90 In the nucleus, THF is required for de novo dTMP biosynthesis, but it is not understood how 5-methyl

91 t a robust source of one-carbons for de novo dTMP biosynthesis.

92 a very rapid decrease in the rate of de novo dTMP formation and, consequently, in intracellular dTTP

93 Furthermore, we show that de novo dTMP synthesis does not occur in the cytosol at rates su

94 1 (SHMT1) expression limits rates of de novo dTMP synthesis in the nucleus.

95 This computational model shows that de novo dTMP synthesis is highly sensitive to the common MTHFR C

96 icate that unlike other nucleotides, de novo dTMP synthesis occurs within mitochondria and is essenti

97 In this study, we identified a de novo dTMP synthesis pathway in mammalian mitochondria.

98 We investigated whether the de novo dTMP synthesis pathway was sensitive to perturbations in

99 ata indicating that impaired nuclear de novo dTMP synthesis results in uracil misincorporation into D

100 evated uracil in DNA, lower rates of de novo dTMP synthesis, and increased salvage pathway dTMP biosy

101 harmacologically induced decrease in de novo dTMP synthesis.

102 accumulation in the cytosol impairs nuclear dTMP biosynthesis.

103 nd Dpo4 incorporated the correct nucleotide (dTMP) opposite the lesion, dGMP and dAMP were inserted w

104 Accordingly, the administration of dTMP-growth hormone fusion protein led to a rapid platel

105 deltaC, dG-N2-TAM promoted small amounts of dTMP and/or dAMP incorporations and deletions.

106 incorporation of dAMP and lesser amounts of dTMP opposite the lesion.

107 r BPDE-DNA adduct, promoted small amounts of dTMP, dAMP, and dGMP misincorporation opposite the lesio

108 The biosynthesis of dTMP has been studied in cell extracts of two different

109 tudied in detail with regard to catalysis of dTMP formation and of thymidylate synthase partial react

110 sii ThyX protein catalyzed the conversion of dTMP from dUMP.

111 x 10(9)/L), in comparison with high doses of dTMP.

112 and tested for activity in the formation of dTMP and the dehalogenation of 5-bromo- and 5-iodo-dUMP.

113 The methyl group of dTMP apparently clashes with a highly conserved tyrosine

114 s investigation the rate of incorporation of dTMP and AZTMP by wild type and mutant HIV-1 RT was dete

115 Pol alpha catalyzed incorporation of dTMP and dAMP opposite epsilon dC, accompanied by lesser

116 s using the strand-specific incorporation of dTMP and dAMP.

117 Pol delta catalyzed incorporation of dTMP and lesser amounts of dAMP and dGMP.

118 d reaction product revealed incorporation of dTMP opposite dG-AAF, accompanied by much smaller amount

119 dA-N6-3MeE promoted the incorporation of dTMP opposite the lesion as well as two-base deletions,

120 -3MeE promoted preferential incorporation of dTMP opposite the lesion with small amounts of incorpora

121 -3MeE promoted preferential incorporation of dTMP, along with incorporation of dCMP and two-base dele

122 2-OHE1-N6-dA also promoted incorporation of dTMP, the correct base, opposite the lesion, accompanied

123 tide was used, preferential incorporation of dTMP, the correct base, was also observed.

124 cts were used, preferential incorporation of dTMP, the correct base, was observed.

125 volved a 1-base deletion or incorporation of dTMP.

126 N2-tamoxifens only promoted incorporation of dTMP.

127 ppears to have a mixed type of inhibition of dTMP kinase.

128 oxidized form of 8-oxoA direct insertion of dTMP by Kf exo-.

129 ch was in turn favored over the insertion of dTMP.

130 osine or misincorporation of dUMP instead of dTMP [4] [5], and it is the primary activity in the DNA

131 when pol delta was used, misincorporation of dTMP (0.52%) was detected.

132 ly, we found substantial misincorporation of dTMP and dAMP opposite 2-AP-6-SCH3 and 2-AP-6-SO3H, resp

133 The preferential misincorporation of dTMP opposite the alpha-dNs could be attributed to the u

134 nied by small amounts of misincorporation of dTMP, dAMP and dGMP.

135 assay were caused by the misincorporation of dTMP.

136 tion that is required for phosphorylation of dTMP.

137 , there was also a significant proportion of dTMP insertions that suggest another mutational pathway

138 those required for the de novo synthesis of dTMP and purine nucleotides and for remethylation of hom

139 MTX inhibits the synthesis of dTMP needed for DNA replication by blocking the conversi

140 g, which has nearly the same rate as that of dTMP incorporation, as estimated from rapid chemical que

141 ly, the mutations had detrimental effects on dTMP synthesis with the triple mutant being completely i

142 courses for the insertion of dCMP, dGMP, or dTMP opposite an abasic site were linear.

143 TMP synthesis, and increased salvage pathway dTMP biosynthesis relative to control fibroblasts.

144 dem dimer of thrombopoietin mimetic peptide (dTMP) on thrombopoiesis, manifested by a significant acc

145 The enzyme phosphorylates dTMP and dGMP to dTDP and dGDP, respectively, in the pre

146 asites possess redundant pathways to produce dTMP, one involving thymidine kinase (TK) and the second

147 ability of thymidylate synthetase to produce dTMP, the drug also has significant effects on RNA metab

148 e correct chirality in the methyl of product dTMP.

149 loss of function on folate-dependent purine, dTMP, and methionine biosynthesis in fibroblasts from th

150 With pol kappa, significant dTMP misincorporation was observed opposite the lesion.

151 tD function under conditions where sustained dTMP synthesis is compromised.

152 )-deficient strains, which cannot synthesize dTMP endogenously.

153 r thymine-deoxythymidine 5'-monophosphate (T-dTMP) but not adenine-deoxyadenosine 5'-monophosphate (A

154 nthesis has a higher metabolic priority than dTMP synthesis.

155 es with pol eta and pol kappa indicated that dTMP, the correct base, was preferentially incorporated

156 Both the dTMP and dGMP kinase reactions are reversible.

157 osphate donor and a positive effector of the dTMP kinase reaction.

158 In M. thermophila, the dTMP was formed from dUMP and [methylene-2H2]-5,10-methy

159 entional thymidylate synthase (TS) for their dTMP requirements.

160 olate-dependent nuclear de novo thymidylate (dTMP) biosynthesis is a sensitive target of arsenic trio

161 ubsequent inhibition of de novo thymidylate (dTMP) biosynthesis.

162 ssociated with impaired de novo thymidylate (dTMP) biosynthesis.

163 indicate that impaired de novo thymidylate (dTMP) synthesis through changes in SHMT expression is ca

164 he process of phosphate transfer from ATP to dTMP, was proposed based on X-ray cocrystal structures,

165 talyzes the reductive methylation of dUMP to dTMP and is essential for the synthesis of DNA.

166 se (TS) catalyzes the methylation of dUMP to dTMP and is the target for the widely used chemotherapeu

167 nthase (TS) catalyzes methylation of dUMP to dTMP and is the target of cancer chemotherapeutic agents

168 45) (TS) catalyzes the conversion of dUMP to dTMP and is therefore indispensable for DNA replication

169 nism is the deficient methylation of dUMP to dTMP and subsequent incorporation of uracil into DNA by

170 thyleneTHF), a donor for methylating dUMP to dTMP in DNA synthesis, to 5-methyltetrahydrofolate (meth

171 CHO) cells and HepG2 cells converted dUMP to dTMP in the presence of NADPH and serine, through the ac

172 talyzes the reductive methylation of dUMP to dTMP using (R)-N(5),N(10)-methylene-5,6,7,8-tetrahydrofo

173 ase, we found that the ratio of HETM-dUMP to dTMP varies as a function of CH(2)H(4)folate concentrati

174 hibiting the enzymatic conversion of dUMP to dTMP.

175 elsewhere in the reaction pathway leading to dTMP synthesis.

176 G was 10-fold more efficient than that with dTMP.

177 ase inhibitor, tetrahydrouridine (THU), with dTMP+dCMP.

178 H2H4folate --> TS x dTMP x H2folate --> TS x dTMP --> TS as predicted previously by others from stead

179 > TS x dUMP x (6R)-5,10-CH2H4folate --> TS x dTMP x H2folate --> TS x dTMP --> TS as predicted previo