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 A dCMP residue was faithfully inserted across the ICL-G by

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

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

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

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

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

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

20 nded to a greater degree than primers with a dCMP or dTMP across from the adduct.

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

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

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

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

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

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

27 nzylamine auxiliary, coupling with activated dCMP and photochemical deprotection, the individual dias

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

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

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

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

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

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

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

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

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

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

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

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

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

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

42 as well as direct incorporation of dAMP and dCMP.

43 nalog dCMPNPP and the products 5-Me-dCMP and dCMP.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

67 appa preferentially incorporated the correct dCMP opposite the branched-chain lesions.

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

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

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

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

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

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

74 deoxycytidine deamination might enhance dTMP+dCMP therapy.

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

76 ncorporates TMP less efficiently than either dCMP or dAMP.

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

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

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

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

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

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

83 and UDP-sugars, while UMK2 is important for dCMP recycling that contributes to mitochondrial DNA sta

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

100 ength products, preferentially incorporating dCMP opposite the lesion.

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

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

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

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

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

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

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

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

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

110 bstrate analog dCMPNPP and the products 5-Me-dCMP and dCMP.

111 dCMP and dUMP tightly but does not methylate dCMP.

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

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

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

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

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

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

118 ncreasing serum deoxycytidine monophosphate (dCMP) levels 52-fold.

119 phate (CMP) and deoxycytidine monophosphate (dCMP), but with different efficiencies.

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

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

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

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

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

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

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

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

128 favored over that of the correct nucleotide, dCMP.

129 preferentially than the correct nucleotide, dCMP.

130 229 forms hydrogen bonds to 3-N and 40NH2 of dCMP.

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

132 4-OHEN-dC, accompanied by lesser amounts of dCMP and dTMP incorporation and base deletion.

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

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

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

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

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

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

139 is by decreasing the catalytic efficiency of dCMP insertion opposite Fapy*dG, thus reducing polymeras

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

141 the binding site for the phosphate group of dCMP.

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

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

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

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

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

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

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

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

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

151 8-bromo-2'-deoxyguanosine, incorporation of dCMP was strongly favored by both enzymes, with no detec

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

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

154 0.5 times greater than the incorporation of dCMP, indicating an average repair patch of 3-4 nucleoti

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

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

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

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

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

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

161 1 s(-1)) were measured for the insertion of dCMP, dGMP, and dTMP opposite the abasic site using sing

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

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

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

165 splacements and further favor methylation of dCMP.

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

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

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

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

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

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

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

173 MP also have potent inhibitory activities on dCMP deaminase.

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

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

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

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

178 No significant insertion of dTTP or dCMP was detected.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

195 beta preferentially inserts dTMP rather than dCMP opposite m6dG.

196 CMP proved to be far better substrates than dCMP.

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

198 Kinetic studies have determined that dCMP incorporation opposite the beta-anomer is ~90 times

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

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

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

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

203 In contrast, the dCMP deaminase DCTD contributes to cell proliferation an

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

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

206 y well tolerated, even in the absence of the dCMP deaminase Dctd that is considered as the main sourc

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

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

209 eversal of substrate specificity from CMP to dCMP.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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