ライフサイエンスコーパス: dCMP

1 dCMP and dTMP were most frequently inserted by hPol iota

2 dCMP was predominantly incorporated opposite the dG-AF a

3 The discovery that the PBCV-1 dCMP deaminase has two activities, together with a previ

4 describes the characterization of the PBCV-1 dCMP deaminase, which produces dUMP, a key intermediate

5 th a 50-fold slower rate than the matched 3'-dCMP.

6 3'-dGMP > 3'-dAMP approximately equal to 3'-dCMP approximately equal to 3'-dTMP.

7 tive rates of exchange following the trend 5'dCMP > 5'-dAMP > 5'dTMP >> 5'-dGMP and 3'-dGMP > 3'-dAMP

8 Whereas both 5'-dCMP and the d(CCCT) quadruplex exhibit a midpoint of ti

9 For 5'-dCMP- and 5'-dTMP-, a comparison of aqueous ionization e

10 For 5'-dCMP- and 5'-dTMP-, the increased favorableness of base

11 ion of 2'-deoxycytosine-5'-monophosphate (5'-dCMP) to show that the spectral fingerprint associated w

12 dTMP-) and 2'-deoxycytidine 5'-phosphate (5'-dCMP-).

13 ble to efficiently and specifically insert a dCMP opposite a DNA template apurinic/apyrimidinic (AP)

14 Human REV1 inserted a dCMP efficiently opposite a template 8-oxoguanine, (+)-t

15 dCMP transferase that specifically inserts a dCMP residue opposite a DNA template G.

16 We show that the human REV1 protein is a dCMP transferase that specifically inserts a dCMP residu

17 th the Lactobacillus caseiTS mutant N229D, a dCMP methylase, revealed that there is a steric clash be

18 tidyl transferase activity which transfers a dCMP residue from dCTP to the 3' end of a DNA primer in

19 base substitution in vivo (e.g. T-dGMP or A-dCMP for T to C transitions), L612M pol delta error rate

20 irs but reduced selectivity for T.dCMP and A.dCMP mispairs.

21 annealed to specific oligonucleotides and AB-dCMP incorporated into DNA by primer extension.

22 photoaffinity labeling by DNA containing AB-dCMP gave results comparable to that with AB-dUMP at pro

23 DNA photoaffinity labeling with AB-dCMP was used to survey protein-DNA contacts in initiati

24 None of the D- and L-dCTP analogs activated dCMP deaminase as dCTP.

25 Thus simply admitting dCMP into the dUMP binding site of TS is not sufficient

26 butable to their inhibitory activity against dCMP deaminase by their phosphorylated metabolites, wher

27 ass all three modified nucleosides; although dCMP was inserted preferentially, we found substantial m

28 Incorporation of dAMP (29%) and dCMP (53%) opposite the abasic lesion at 37 degrees C co

29 rase, dAMP (22%), TMP (16%), dGMP (5.3%) and dCMP (1.2%) were all incorporated opposite ethano-dC, al

30 tudy, BPQ adducts of dGMP(3'), dAMP(3'), and dCMP(3') were prepared.

31 ructure, complemented by structures apo- and dCMP-bound, provide insights into the allosteric mechani

32 y catalyzing the conversion of UMP, CMP, and dCMP into their diphosphate form.

33 tidine-5'-monophosphate, d-CpC, d-CpCpC, and dCMP residues in DNA resulted in at least 26 distinguish

34 Consistent with previous reports, dAMP and dCMP are inserted selectively opposite 8-oxoG with all t

35 Pol eta promoted incorporation of dAMP and dCMP at the dA-N(6)-3MeE lesion, while with pol kappaDel

36 sites for the enzyme by deaminating dAMP and dCMP in DNA to dIMP and dUMP, respectively.

37 served, along with incorporation of dAMP and dCMP opposite the lesion.

38 ypassed the lesion by incorporating dAMP and dCMP, respectively, opposite the lesion and extended pas

39 as well as direct incorporation of dAMP and dCMP.

40 d the preferential incorporation of dGMP and dCMP opposite the N(2)-Et-dG lesion, accompanied by a sm

41 This substrate was designed so that dGMP and dCMP were exclusively incorporated into the leading and

42 olymerase kappa (Pol kappa) inserts dGMP and dCMP within the [T](11) mononucleotide repeat, producing

43 amounts of incorporation of dAMP, dGMP, and dCMP opposite the lesion.

44 tures are also uniquely occupied by dTMP and dCMP resolving aspects of substrate specificity.

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

46 Rev1, an essential TLS scaffold protein and dCMP transferase, inhibits both cisplatin- and cyclophos

47 The correct base, dCMP, was incorporated opposite HOPdG in all circumstanc

48 The correct base, dCMP, was incorporated preferentially opposite 8-amino-d

49 ctive site, and the mutant enzyme binds both dCMP and dUMP tightly but does not methylate dCMP.

50 hat the same active site is involved in both dCMP and dCTP deaminations.

51 st, the Y567A mutant of RB69pol inserts both dCMP and dAMP opposite 8-oxoG rapidly and with equal eff

52 d that the position and orientation of bound dCMP closely approaches that of dUMP in wild-type TS, wh

53 Q-dGMP adduct, 2 BPQ-dAMP adducts, and 3 BPQ-dCMP adducts.

54 The BPQ-dGMP, BPQ-dAMP, and BPQ-dCMP adduct standards were used in 32P postlabeling stud

55 ies of the novel BPQ-dGMP, BPQ-dAMP, and BPQ-dCMP adducts were confirmed by acid phosphatase dephosph

56 Surprisingly, Dpo4 generates C.dCMP mismatches at an unusually high average rate and pr

57 veals that WRN improves hpol kappa-catalyzed dCMP insertion opposite 8-oxo-dG approximately 10-fold a

58 The primer containing dCMP was further excised, and by 40 min, more than 75% o

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

60 of pol iota and/or REV1 in inserting correct dCMP opposite alpha-OH-PdG during error-free synthesis.

61 ta was used, direct incorporation of correct dCMP was primarily observed, accompanied by small amount

62 ncorrect purine nucleotides over the correct dCMP and hence can be mutagenic.

63 ng repair toward long-patch BER upon correct dCMP incorporation, thus enhancing repair efficiency.

64 ated forms of the four mononucleotides dAMP, dCMP, dGMP, and dTMP was studied experimentally by equil

65 leting the Schizosaccharomyces pombe dcd1(+) dCMP deaminase gene (SPBC2G2.13c) increases dCTP approxi

66 ductase (RNR) and deoxycytidylate deaminase (dCMP deaminase) are pivotal allosteric enzymes required

67 A deoxycytidylate (dCMP) deaminase encoded in T4-bacteriophage DNA that is

68 ults support a major role for Rev1-dependent dCMP insertion across from AP sites and a lesser role fo

69 deoxycytidine deamination might enhance dTMP+dCMP therapy.

70 nhibitor, tetrahydrouridine (THU), with dTMP+dCMP.

71 o the damaged DNA when the photoreactive FAP-dCMP (exo-N-{2-[N-(4-azido-2,5-difluoro-3-chloropyridin-

72 When the FAP-dCMP analogue is located to the 3' side of the adduct, n

73 The efficiency of gap-filling dCMP insertion opposite the adduct was diminished by >6

74 from 1.5 x 10(-)(5) microM(-)(1) s(-)(1) for dCMP opposite templating C to 2 x 10(-)(3) microM(-)(1)

75 e negative values (< or =-12 kcal mol-1) for dCMP, dGMP, and dTMP and the least negative value for dA

76 ecule binds to the charge-carrying group for dCMP, dGMP, and dTMP.

77 the active sites of human UMP/CMP kinase for dCMP and for CMP cannot be identical.

78 zyme has a higher affinity for dCTP than for dCMP, (ii) dCTP serves as a positive heterotropic effect

79 Furthermore, dCMP insertion was greatly preferred regardless of the s

80 iency was as follows: arabinofuranosyl-CMP > dCMP > beta-L-2',3'-dideoxy-3'-thia-CMP > Gemcitabine mo

81 abasic sites follows the order dAMP > dGMP > dCMP > dTMP.

82 creases in the order of dAMP > dGMP > dTMP > dCMP, from a high of 5.8 when dAMP is to be inserted fol

83 ion followed the order: dAMP > dGMP > dTMP > dCMP, which did not correlate with the mutational spectr

84 As predicted, the recombinant protein has dCMP deaminase activity that is activated by dCTP and in

85 of plasmid pSP189 was labeled with [5-(125)I]dCMP at position 15.

86 pectedly, however, a significant increase in dCMP.A and dGMP.A mispairs was also observed at the "ups

87 Both pol eta and pol kappa incorporated dCMP, the correct base, opposite dG-N(2)-AAF.

88 DNA polymerase iota incorporates dCMP opposite N2-ethyl-Gua and unadducted Gua with simil

89 tidyl transferase activity that incorporates dCMP into DNA and its ability to function as a scaffold

90 dyl transferase activity, which incorporates dCMP opposite abasic sites in the DNA template, and that

91 paDeltaC was more efficient at incorporating dCMP opposite the dG-N(2)-3MeE lesion than pol eta.

92 adduct than that of pol eta by incorporating dCMP, a correct base, opposite the adduct.

93 ength products, preferentially incorporating dCMP opposite the lesion.

94 studies demonstrated that CMP could inhibit dCMP phosphorylation in a noncompetitive manner, with Ki

95 cteriophage RB69 (RB69pol) prefers to insert dCMP as opposed to dAMP when situated opposite 8-oxoG by

96 wed that both pol kappa and pol eta inserted dCMP and dAMP opposite the 4-OHEN-dC and extended past t

97 cts as a deoxycytidyl transferase, inserting dCMP opposite lesions.

98 the L-deoxycytidine analogs may not involve dCMP deaminase directly.

99 C-terminal 205 aa of Rev1 did not affect its dCMP transferase activity, but abolished its stimulatory

100 on in translesion synthesis, the role of its dCMP transferase activity remains uncertain.

101 In addition to its dCMP transferase, a non-catalytic function of Rev1 is su

102 the circular parts of the substrates lacked dCMP; thus, no dCTP was required for leading-strand synt

103 dCMP and dUMP tightly but does not methylate dCMP.

104 CD) converts deoxycytidine 5'-monophosphate (dCMP) to deoxyuridine 5'-monophosphate and is a major su

105 e product 2'-deoxycytidine-5'-monophosphate (dCMP) to m5dCMP.

106 f CMP, UMP, and deoxycytidine monophosphate (dCMP) and also plays an important role in the activation

107 e TK2 products, deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs

108 nthase (TS) and deoxycytidine monophosphate (dCMP) deaminase by dZMP, which deprives cells of essenti

109 ate constant of deoxycytidine monophosphate (dCMP) insertion opposite the first tetrad-guanine by hRe

110 In TS N229D.dCMP, Asp-229 forms hydrogen bonds to 3-N and 40NH2 of d

111 between gp32 and RNR and NDP kinase, but not dCMP hydroxymethylase, deoxyribonucleoside monophosphate

112 dCDP but not dCMP or dCyd could inhibit the transport activity.

113 late synthase (TS) methylates only dUMP, not dCMP.

114 We also report a nucleotide (dCMP)-bound crystal structure that informs a multistep m

115 n between the newly incorporated nucleotide (dCMP or dAMP) and the templating 8-oxoG.

116 eferentially inserts the correct nucleotide, dCMP, opposite N(2)-CEdG lesions.

117 ver the insertion of the correct nucleotide, dCMP, which was in turn favored over the insertion of dT

118 favored over that of the correct nucleotide, dCMP.

119 preferentially than the correct nucleotide, dCMP.

120 229 forms hydrogen bonds to 3-N and 40NH2 of dCMP.

121 epsilon dC, accompanied by lesser amounts of dCMP and dGMP and some two-base deletions.

122 4-OHEN-dC, accompanied by lesser amounts of dCMP and dTMP incorporation and base deletion.

123 -AAF, accompanied by much smaller amounts of dCMP, dAMP, and dGMP and some one- and two-base deletion

124 d promoted incorporation of small amounts of dCMP, dAMP, and dTMP opposite the lesion.

125 ite the lesion, along with lesser amounts of dCMP, the correct base.

126 Consequently, 6-C of dCMP is over 4 A from the active site sulfhydryl.

127 late deaminase, catalyzing the conversion of dCMP to dUMP, is an important enzyme in the de novo synt

128 ctivates checkpoint responses, the effect of dCMP deaminase deficiency is largely unknown.

129 Second, two mutant form of dCMP deaminase (H90N and H94N), altered in presumed zinc

130 the binding site for the phosphate group of dCMP.

131 elta, 2-OHE1-N2-dG promoted incorporation of dCMP (6.3 and 3.1%, respectively), the correct base, opp

132 Pol alpha catalyzed incorporation of dCMP and dAMP opposite all four stereoisomers of dG-N2-t

133 Pol beta promoted incorporation of dCMP and dAMP, along with small amounts of one-base and

134 esion with small amounts of incorporation of dCMP and deletions.

135 oration of dTMP, along with incorporation of dCMP and two-base deletions.

136 dG-AAF promote preferential incorporation of dCMP at the site of the lesion; misincorporation of dAMP

137 d 40%, respectively, of the incorporation of dCMP compared with normal extracts, but extracts from an

138 creases linearly, while the incorporation of dCMP exhibits a distinct lag.

139 a wrong nucleotide, whereas incorporation of dCMP opposite the cross-linked G was 10-fold more effici

140 8-bromo-2'-deoxyguanosine, incorporation of dCMP was strongly favored by both enzymes, with no detec

141 elta catalyzed preferential incorporation of dCMP, a correct base, opposite the lesions; one of the t

142 sing pol beta, preferential incorporation of dCMP, along with small amounts of incorporation of dAMP

143 0.5 times greater than the incorporation of dCMP, indicating an average repair patch of 3-4 nucleoti

144 roducts showed preferential incorporation of dCMP, the correct base, opposite all four stereoisomeric

145 Preferential incorporation of dCMP, the correct base, was observed opposite all 2-OHE-

146 to dG-C8-PhIP, preferential incorporation of dCMP, the correct base, was observed opposite the dG-C8-

147 Preferential incorporation of dCMP, the correct base, was observed opposite the dG-N2-

148 miscoding spectra; direct incorporations of dCMP and dAMP were observed, along with lesser amounts o

149 -->dC (1%), indicating that the insertion of dCMP opposite the adduct is predominant.

150 1 s(-1)) were measured for the insertion of dCMP, dGMP, and dTMP opposite the abasic site using sing

151 eady-state time courses for the insertion of dCMP, dGMP, or dTMP opposite an abasic site were linear.

152 lanation for the preferential methylation of dCMP instead of dUMP by this mutant.

153 11) change in specificity for methylation of dCMP versus dUMP.

154 splacements and further favor methylation of dCMP.

155 e of TS is not sufficient for methylation of dCMP.

156 V were essential for the misincorporation of dCMP opposite these minor-groove DNA lesions, whereas on

157 nt effect of dCTP, an allosteric modifier of dCMP deaminase, upon the interactions.

158 As a result, the cytosine moiety of dCMP is displaced from the active site and the catalytic

159 there is a steric clash between the 4-NH2 of dCMP and His 199, a residue which normally H-bonds to th

160 ue 199 which did not impinge on the 4-NH2 of dCMP should correct the displacements and further favor

161 must be involved to make phosphorylation of dCMP or pyrimidine analog monophosphates inside cells by

162 MP also have potent inhibitory activities on dCMP deaminase.

163 t frequently inserted by hPol iota, and only dCMP was inserted by Rev1.

164 sence of oxygen had little effect with dC or dCMP but had quantitative and qualitative effects with d

165 hen primers terminated with either dFdCMP or dCMP were used as substrates, normal primer was hydrolyz

166 '-penultimate dFdC monophosphate (dFdCMP) or dCMP by the 3'-->5' exonuclease of the Klenow fragment.

167 No significant insertion of dTTP or dCMP was detected.

168 al structures of binary complexes of dUMP or dCMP with the Lactobacillus caseiTS mutant N229D, a dCMP

169 involved in dNTP biosynthesis (e.g., RNR or dCMP deaminase).

170 immobilized enzyme (either dTMP synthase or dCMP deaminase), and the specifically bound proteins wer

171 strate for purified enzyme than CMP, UMP, or dCMP.

172 nsertions opposite dG-AAF followed the order dCMP > dAMP > dGMP > dTMP; the frequency of dNTP inserti

173 opposite 8-oxo-dG was slightly favored over dCMP depending on "downstream" sequence context.

174 to primers containing either 3'-penultimate dCMP or dFdCMP were used to evaluate excision during DNA

175 binant human UMP/CMP kinase to phosphorylate dCMP and CMP (referred as dCMPK and CMPK activities).

176 t the lesion by incorporating preferentially dCMP, the correct base, opposite the lesion, accompanied

177 dicated by the formation of terminal protein-dCMP complex, and elongation of > 300 nucleotides.

178 translesion synthesis, we separated the Rev1 dCMP transferase activity from its non-catalytic functio

179 show that the catalytic function of the Rev1 dCMP transferase is required in a lesion-specific manner

180 e require the catalytic function of the Rev1 dCMP transferase, in contrast to those of UV lesions, wh

181 tic agents (eg, cystathionine beta synthase, dCMP deaminase, and CTP synthase).

182 .dGMP mispairs but reduced selectivity for T.dCMP and A.dCMP mispairs.

183 ulting in formation of primers with terminal dCMP or dFdCMP.

184 beta preferentially inserts dTMP rather than dCMP opposite m6dG.

185 CMP proved to be far better substrates than dCMP.

186 e abasic sites in the DNA template, and that dCMP insertion is the major event during bypass of an ab

187 Steady-state kinetic data indicate that dCMP is efficiently inserted opposite all dG-N(2)-BPDE a

188 ngle nucleotide incorporation indicates that dCMP is most frequently inserted by hPol kappa opposite

189 ly purified human UMP/CMP kinase showed that dCMP, as well as pyrimidine analog monophosphates, were

190 By combining the dCMP insertion activity of human REV1 with the extension

191 as a positive heterotropic effector for the dCMP deaminase activity and a positive homotropic effect

192 y, and (iii) the enzymatic efficiency of the dCMP deaminase activity is about four times higher than

193 After 5 min, more than one-half of the dCMP primers were extended, whereas only 15% had been ex

194 o and orientation the could hydrogen bond to dCMP by a hydrogen bond network between conserved residu

195 eversal of substrate specificity from CMP to dCMP.

196 ed life span of Tk2(-/-) animals compared to dCMP+dTMP.

197 alized DNA polymerase that may contribute to dCMP insertion opposite many types of DNA damage during

198 Damage to dC, d-CpC, and d-CpCpC but not to dCMP or DNA was largely quenched by ethanol, indicating

199 -)-BPDE-N2-dG adducts pair preferentially to dCMP and dAMP during translesional synthesis in a proces

200 recombinant cN-I showed high affinity toward dCMP and lower affinity toward AMP and IMP.

201 synthesis the viral DNA polymerase transfers dCMP onto the adenovirus preterminal protein, to which i

202 The crystal structure of TS.dCMP shows sCMP 4-NH2 excluded from the space between As

203 inserted following a T to a low of 0.5 when dCMP is to be inserted following a C.

204 -T (6-4) UV photoproduct, a process in which dCMP incorporation occurs only very rarely, indicating t

205 preferentially remove l-OddCMP compared with dCMP from the 3' termini of DNA in human cells.

206 structures of TS H199A/N229D in complex with dCMP and dUMP confirmed that the position and orientatio

207 ight of the mutation pattern consistent with dCMP insertion observed earlier in mouse fibroblast cell

208 ng primarily one- or two-base deletions with dCMP, the correct base, incorporated opposite dG-AF.

209 Their interaction with dCMP deaminase as a monophosphate or a triphosphate meta

210 g that iron is strongly associated only with dCMP and DNA.