ライフサイエンスコーパス: Pol alpha

1 s catalyzed by DNA polymerase alpha/primase (pol alpha).

2 h the Pol12 subunit of DNA polymerase alpha (Pol alpha).

3 ith MCM2-7, and with the p180 subunit of DNA pol alpha.

4 litating RNA primer handover from primase to Pol alpha.

5 r of primers from the primase active site to pol alpha.

6 ng that Dna2 acts in a process that involves Pol alpha.

7 t provide the proof-reading function for DNA pol alpha.

8 f p53 to enhance the replication fidelity of pol alpha.

9 phosphorylation and chromatin association of pol alpha.

10 ming and DNA polymerizing activities of Prim-Pol alpha.

11 hidicolin failed to improve its affinity for Pol alpha.

12 the DNA primase-polymerase in eukaryotes is pol alpha.

13 aRPA is unable to support de novo priming by pol alpha.

14 plicative polymerases, exonuclease-deficient Pol alpha.

15 n and 3D architecture of heterodimeric yeast Pol alpha.

16 d (ss) DNA and the catalytic p180 subunit of pol alpha.

17 ed efficiently by Pol-zeta, but not by yeast Pol-alpha.

18 we examined how human DNA polymerase alpha (pol alpha), a B family enzyme, and DNA polymerase from B

19 In contrast, DNA polymerase alpha (Pol alpha) accumulates to higher than normal levels at s

20 tor blocks binding of dCTP by docking at the Pol alpha active site and by rotating the template guani

21 ned so as to block nucleic acid entry to the Pol alpha active site.

22 RT - PCR analysis and pol alpha activity assays revealed the presence of pol a

23 We propose Stn1 normally promotes Pol alpha activity at telomeres but can be recruited thr

24 Because pol alpha activity is essential for both initiation and

25 abasic lesion bypass during primase-coupled pol alpha activity provides an additional mechanism for

26 oducts generated during this primase-coupled pol alpha activity showed that dAMP was preferentially i

27 disrupt the association between primase and pol alpha allowed us to assess the physiological signifi

28 Pol alpha also polymerized 8-oxo-dGTP across from a temp

29 anied by misincorporation of dCTP (0.54% for pol alpha and 3.2% for pol delta) and one-base deletion

30 ir or lagging strand synthesis together with Pol alpha and Ctf4, in a role that is optimal with, but

31 and activity and essentially all of the DNA pol alpha and delta activities exclusively cosedimented

32 ined its DNA binding activity, but inhibited pol alpha and delta activity.

33 h the Pol alpha N-terminal domain, promoting Pol alpha and delta binding to stalled replication forks

34 Using pol alpha and delta, 2-OHE1-N2-dG promoted incorporation

35 P) by antisense RNA expression downregulates pol alpha and E2F-1 expression during early S phase.

36 xamine the role of PARP in the regulation of pol alpha and E2F-1 gene expression, we utilized immorta

37 uding the simultaneous association with both Pol alpha and GINS.

38 we identify new Ctf4 partners in addition to Pol alpha and helicase, all of which contain a "Ctf4-int

39 owever, it does not interact with the mutant pol alpha and is delocalized away from the silent mat lo

40 Both pol alpha and KF polymerized the analogues up to 140-fol

41 Both pol alpha and Klenow fragment exhibit a remarkable inabi

42 Whereas pol alpha and Klenow fragment exhibited minimal discrimi

43 ty alone cannot account for the inability of pol alpha and Klenow fragment to discriminate against un

44 overn the incorporation of dNTPs into DNA by pol alpha and Klenow fragment.

45 ositively regulates transcription of the DNA pol alpha and PCNA genes; thus, PARP may be necessary fo

46 3'-primer terminus in reactions catalyzed by pol alpha and pol beta was established by steady-state k

47 In addition, with pol alpha and pol beta, large amounts of 5-base deletion

48 Also like pol alpha and pol beta, pol epsilon exhibits induced dNT

49 constitutes a block during DNA synthesis by pol alpha and pol beta.

50 d two base deletions were also observed with pol alpha and pol beta.

51 idicolin is a very specific inhibitor of DNA pol alpha and pol delta, our results suggest that this c

52 gic studies suggest that in contrast to both pol alpha and pol delta, pol epsilon functions more effi

53 e that like DNA polymerases alpha and delta (pol alpha and pol delta, respectively), free pol epsilon

54 its catalytic properties in comparison with Pol alpha and Pol delta.

55 and to markedly stimulate the activities of Pol alpha and Pol epsilon.

56 In the complex, Pol alpha and primase cooperate in the production of RNA

57 It tethers Pol alpha and primase, facilitating RNA primer handover

58 mational change for nucleic acid delivery to Pol alpha and subsequent DNA synthesis.

59 Critically, Pol alpha and the CMG helicase share a common mechanism

60 o-terminal tails of the catalytic subunit of Pol alpha and the Sld5 subunit of GINS contain a conserv

61 In fission yeast both DNA polymerase alpha (pol alpha) and delta (pol delta) are required for DNA ch

62 them as substrates for DNA polymerase alpha (pol alpha) and Klenow fragment (exo-) of DNA polymerase

63 kened interaction with DNA polymerase alpha (pol alpha) and that aRPA is not able to efficiently stim

64 have found that human DNA polymerase alpha (pol alpha) and the Klenow fragment of Escherichia coli D

65 n, specifically blocks DNA polymerase alpha (Pol-alpha) and Ctf4 recruitment without affecting DNA po

66 hRPA exhibited decreased binding to ATM, DNA pol alpha, and DNA-PK as compared to unphosphorylated re

67 chromatin after Mcm10, concurrently with DNA pol alpha, and is required for efficient DNA synthesis.

68 mation of adenine:hypoxanthine base pairs by pol alpha, and N3 of dATP again helps prevent polymeriza

69 urther dNTPs onto the just added nucleotide, pol alpha appears to monitor the shape of the base pair

70 esized by primase-DNA polymerase alpha (Prim-Pol alpha) are needed to start DNA replication by the re

71 se (HIV RT) and human DNA polymerases alpha (pol alpha), beta (pol beta), gamma (pol gamma), and epsi

72 0p containing amino acids 1-416 retained the pol alpha binding activity, whereas the C terminus, amin

73 both the single-stranded DNA binding and the pol alpha binding properties of Mcm10p play important ro

74 inity, and the equivalent peptide from human Pol alpha binds primase in an analogous fashion.

75 to continue the functional dissection of DNA pol alpha biochemistry at the molecular level.

76 ory effect on pol epsilon, but could inhibit pol alpha by 10-20% at 20 micro M.

77 thesizes a primer that DNA polymerase alpha (pol alpha) can readily elongate, further primase activit

78 The C terminus of the Pol alpha catalytic subunit (p180C) in complex with the

79 Pol alpha catalyzed incorporation of dCMP and dAMP oppos

80 Pol alpha catalyzed incorporation of dTMP and dAMP oppos

81 primase activity and DNA polymerase alpha- (pol alpha) catalyzed elongation of primase-synthesized p

82 lex DNA, TRF1 was also capable of inhibiting pol alpha-catalyzed DNA synthesis on nontelomeric DNA se

83 In contrast, previous analyses of pol alpha-catalyzed elongation of exogenously supplied D

84 s in degradation of the catalytic subunit of pol-alpha, Cdc17/Pol1, regardless of whether cells are i

85 we suggest that Cdc6p overproduction resets pol alpha chromatin binding by a mechanism which is inde

86 of Cdc6 has been deleted is unable to drive pol alpha chromatin binding.

87 the differences between the human and yeast Pol alpha complexes.

88 The partial loss of replication, CMG, or Pol-alpha control provides a potential molecular explana

89 L868M pol alpha copies DNA in vitro with normal activity and p

90 Pol alpha could use beta-L-Fd4CTP as a substrate, but on

91 that at G(1)/S arrest and early in S phase, Pol alpha, delta, and epsilon were associated with the s

92 Pol alpha, delta, and epsilon were released from these o

93 ated action of three DNA polymerases (Pols), Pol alpha, delta, and epsilon.

94 e presence of both DNA replication proteins (Pol alpha, delta, straightepsilon, PCNA, RFC, RFA, DNA l

95 Mutation rates in the Pol alpha, -delta, and -epsilon mutant strains are incre

96 the conserved NS/VxYG motif in region III in Pol alpha, -delta, or -epsilon are viable and a strain w

97 Therefore, Pol epsilon and Pol alpha/delta seem to pursue their functions at least

98 xes, whereas in late S phase Pol epsilon and Pol alpha/delta were largely associated with distinct co

99 s, but in late S phase only Pol epsilon, not Pol alpha/delta, remained associated with lamins.

100 RB69 DNA polymerase (gp43), a member of the pol alpha DNA polymerase family, was examined for its ro

101 the MRC, including DNA polymerase alpha (DNA pol alpha), DNA topoisomerase I (topo I), and proliferat

102 This approach identifies DNA pol alpha, DNA pol delta, DNA pol varepsilon, MCM2-7, Cd

103 In contrast, expression of DNA pol alpha, DNA primase, and RPA was down-regulated in PA

104 f the newly inserted bases lack N-1 and N-6, pol alpha does not efficiently polymerize the next corre

105 of pol delta proofreads errors generated by pol alpha during initiation of Okazaki fragments.

106 ng strand, Pol delta corrects errors made by Pol alpha during Okazaki fragment initiation.

107 With pol alpha, eta and kappa, incorrect dTMP was preferentia

108 ich then positively regulates both E2F-1 and pol alpha expression, when quiescent cells reenter the c

109 The 2.25 A resolution crystal structure of a pol alpha family (family B) DNA polymerase from the hype

110 The wild-type (wt) pol alpha family DNA polymerase from bacteriophage RB69

111 The wild-type (wt) pol alpha family DNA polymerase from bacteriophage RB69

112 ata indicate that, like other members of the pol alpha family of DNA polymerases, the adenovirus DNA

113 ophage RB69 gp43, a member of the eukaryotic pol alpha family of replicative DNA polymerases, shares

114 ) provides new insight into the mechanism of pol alpha family polymerases that include essentially al

115 st a common fidelity mechanism for pol I and pol alpha family polymerases.

116 and editing exonuclease activities unique to pol alpha family polymerases.We suggest that the NH(2)-t

117 ave determined the crystal structures of the pol alpha family RB69 DNA polymerase with DNA containing

118 topologically similar to the two other known pol alpha family structures (bacteriophage RB69 and the

119 A motion provides a model for editing in the pol alpha family.

120 The 45 MDSs in the DNA pol alpha gene are non-randomly scrambled into an odd/ev

121 The remarkably scrambled DNA pol alpha gene must be extensively cut, re-ordered and s

122 On DNA templates containing dG-AAF, pol alpha generated two-base deletions and promoted inco

123 om scrambled patterns in the alphaTP and DNA pol alpha genes are explained by multiple, simultaneous

124 islocalized Stn1 may inappropriately promote Pol alpha in a manner that interferes with Rad53 effecto

125 al structures of the catalytic core of yeast Pol alpha in unliganded form, bound to an RNA primer/DNA

126 es the stability of the catalytic subunit of pol-alpha in budding yeast and human cells.

127 Cdc17, the catalytic subunit of pol-alpha in yeast, is rapidly degraded after depletion

128 talytic subunit of DNA polymerase alpha (DNA pol alpha) in the ciliate Oxytricha nova.

129 atalytic core of human DNA polymerase alpha (Pol alpha) in the ternary complex with an RNA-primed DNA

130 DNA pol alpha incorporated CdATP and ara-CTP with high affin

131 interferes with the loading of And-1 and of pol alpha, inhibiting DNA synthesis.

132 proofreading-deficient DNA polymerase alpha (Pol alpha) initiates Okazaki fragment synthesis with low

133 hat tethering of primase to the replisome by pol alpha is critical for the normal action of DNA repli

134 Pol alpha is enriched at extending Okazaki fragments of

135 Furthermore, we show that pol-alpha is also directly required for Rad9 loading.

136 here that the interaction between Mcm10 and pol-alpha is conserved in human cells.

137 synthesized by error-prone polymerase-alpha (Pol-alpha) is retained in vivo, comprising approximately

138 se-polymerase complex, DNA polymerase alpha (pol alpha), is brought to the origins is still unclear.

139 on of genes required for S phase such as DNA pol alpha, is regulated by interactions with Rb and by c

140 ments for the homologous amino acid in yeast Pol alpha (L868M/F) and Pol delta (L612M), these data in

141 polymerase directly, but is connected to the Pol alpha lagging-strand polymerase by the trimeric adap

142 nclude that the inability of aRPA to support pol alpha loading causes aRPA to be defective in DNA rep

143 ed mechanism of nucleotide polymerization by Pol alpha might contribute to genomic stability by limit

144 The Pol alpha mutant has no obvious phenotype.

145 One pol alpha mutation, pol1-1, destabilizes the orientation

146 Rad51 directly interacts with the Pol alpha N-terminal domain, promoting Pol alpha and del

147 Although neither pol alpha nor KF readily polymerized a natural dNTP oppo

148 fect of WRN is limited to pol delta; neither pol alpha nor pol epsilon can traverse template d(CGG)(n

149 s still essential for MAT switching, neither Pol alpha nor primase was required.

150 synthesis, suggesting that in the absence of pol alpha, normal coordination between S phase and mitos

151 the mechanism by which Mcm10 interacts with pol alpha on and off DNA is unclear.

152 le to efficiently stimulate DNA synthesis by pol alpha on aRPA-coated DNA.

153 Primer extension reactions catalyzed by pol alpha or beta in the presence of four dNTPs were ret

154 Primer extension reactions catalyzed by pol alpha or beta were strongly retarded at the 8-NO(2)-

155 aC were at least 8 times higher than that of pol alpha or beta.

156 Pol epsilon is distinct from that of L868M/F Pol alpha or L612M Pol delta, implying that each polymer

157 nalysis of fully extended products formed by pol alpha or pol beta.

158 (Kf exo-), calf thymus DNA polymerase alpha (pol alpha) or human DNA polymerase beta (pol beta).

159 itive alleles of PCNA, DNA polymerase alpha (Pol alpha), or primase showed that these mutations inhib

160 echanisms and to reveal the details of human Pol alpha organization, we determined the crystal struct

161 nd we observed that the catalytic subunit of pol-alpha, p180, was degraded with similar kinetics as M

162 he interaction between the subunits of yeast pol alpha, particularly p167 and p79, using a yeast two-

163 A second group of polymerases (Pol alpha, Pol beta, and T7(-)) fails to extend all non-

164 tivity of the multi-subunit DNA polymerases: Pol alpha, Pol delta and Pol epsilon.

165 es minimally three B-family DNA polymerases: Pol alpha, Pol delta, and Pol .

166 ases, polymerases alpha, delta, and epsilon (Pol alpha, Pol delta, and Pol epsilon), are responsible

167 ukaryotic replicative DNA polymerases (pol): pol alpha, pol delta, and pol epsilon.

168 nds by the three replicative DNA polymerases Pol alpha, Pol delta, and Pol epsilon; and canonical mat

169 replication mutations, including alleles of pol alpha, pol delta, pol epsilon, and PCNA (proliferati

170 A strain with this substitution in Pol alpha (pol1-Y869A) is viable, but it exhibits slow g

171 not by co-overexpression of the B-subunit of pol-alpha, Pol12.

172 Their ability to stimulate pol alpha polymerase activity and bind to single-strande

173 derivatives lost their ability to stimulate pol alpha polymerase activity and bind to single-strande

174 These results therefore suggest that the pol alpha polymerases undergo a series of conformational

175 es significantly decreases the rate at which pol alpha polymerizes the resulting bases opposite A, C,

176 ssDNA-binding complex, may regulate primase-Pol alpha (PP) activity at telomeres constitutively, and

177 l function of the CST complex is its primase-Pol alpha (PP) stimulatory activity.

178 While pol alpha preferentially incorporated the analogues oppo

179 ct physically with the DNA polymerase-alpha (pol-alpha).primase complex.

180 The DNA Polymerase alpha (Pol alpha)/primase complex initiates DNA synthesis in eu

181 places the leading Pol epsilon below CMG and Pol alpha-primase at the top of CMG at the replication f

182 within both the context of the four-subunit pol alpha-primase complex and in the p49-p58 primase com

183 10p activates the polymerase activity of the pol alpha-primase complex by generating truncated deriva

184 studies provide additional evidence that the Pol alpha-primase complex can initiate DNA synthesis onl

185 findings, Mcm10p facilitated the binding of pol alpha-primase complex to primed DNA and formed a sta

186 gen (T-ag)-dependent RNA primer synthesis by pol alpha-primase complex was observed among the heterol

187 nd stimulates DNA synthesis catalyzed by the pol alpha-primase complex with various primed DNA templa

188 ngs together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker betwe

189 gest that the interaction of Mcm10p with the pol alpha-primase complex, its binding to single-strande

190 elongation of primase-synthesized primers by pol alpha-primase is fundamentally different than elonga

191 primed DNA and formed a stable complex with pol alpha-primase on primed templates.

192 resting cells in S phase using ts alleles of Pol alpha-primase, prior to inducing the DSB, sequesters

193 lease of the completed RNA-DNA primer by the Pol alpha/primase complex simplifies current models of p

194 Pol alpha/primase initiates primers on both strands that

195 oth 180- (p180) and 70-kDa (p70) subunits of pol alpha/primase interact with HPV-11 E1.

196 otein E1 and human polymerase alpha/primase (pol alpha/primase) subunits.

197 The pol-alpha:primase binding domain in p12(DOC-1) is mapped

198 ated either by a direct inhibitory effect on pol-alpha:primase or by its effect on cyclin-dependent k

199 r of DNA replication by direct inhibition of pol-alpha:primase or by negatively regulating the CDK2-m

200 The biological effect of p12(DOC-1) on pol-alpha:primase was examined using in vitro DNA replic

201 ssociates with DNA polymerase alpha/primase (pol-alpha:primase) in vitro and in cells.

202 stimulate DNA replication by phosphorylating pol-alpha:primase.

203 ulating the CDK2-mediated phosphorylation of pol-alpha:primase.

204 suppresses CDK2-mediated phosphorylation of pol-alpha:primase.

205 Using pol alpha, primer extension reactions were blocked at dG

206 ating spores disrupted for the gene encoding pol alpha rapidly enter mitosis in the absence of DNA sy

207 enzimidazole-derived bases (i.e., bases that pol alpha rapidly incorporates opposite all four natural

208 We also detected diminished GINS and pol-alpha recruitment to the Mcm2-7 complex.

209 ring primase to the eukaryotic replisome via pol alpha remain poorly characterized.

210 single-stranded DNA templates, but not when pol alpha replaced pol beta.

211 f mammalian flap endonuclease (FEN1) excises Pol alpha replication errors in a MutSalpha-dependent, M

212 extension of primase-synthesized primers by pol alpha resulted in 60-93% bypass of abasic lesions.

213 The EM reconstructions of Pol alpha reveal a bilobal shape with separate catalytic

214 d interaction analysis of the p79 subunit of pol alpha revealed a complementary region with two subdo

215 -independent mismatch repair process we call Pol alpha-segment error editing (AEE).

216 In contrast, pol alpha shows no propensity for this type of synthesis

217 l and computational data to demonstrate that Pol alpha specifically recognizes the A-form RNA/DNA hel

218 ion in vitro, whereas mutant RPA that lacked pol alpha stimulatory activity (including the zinc-finge

219 that RPA's DNA binding activity, but not its pol alpha stimulatory activity, is required for DNA repl

220 Pol alpha strongly discriminated against polymerizing dA

221 Pol alpha strongly favors incorporation of dAMP directly

222 Thus far, the other apo-pol alpha structures that have been determined adopt ope

223 ar kinetics as Mcm10, whereas the regulatory pol-alpha subunit, p68, remained unaffected.

224 nt polymerases with even lower fidelity than pol alpha, such intermolecular proofreading could be rel

225 The catalytic subunits of primase and pol alpha synthesize composite RNA-DNA primers that init

226 rriers to Pol-delta-mediated displacement of Pol-alpha-synthesized DNA, resulting in incorporation of

227 conserved motif at the extreme C terminus of pol alpha that is critical for interaction of the yeast

228 , which is controlled by TopBP1 and includes pol-alpha, that mediates the loading of the 9-1-1 comple

229 Antisera specific against the four-subunit pol alpha, the catalytic subunit of pol delta, and the M

230 detail the mode of association of primase to Pol alpha, the critical interaction that keeps primase t

231 We show now that Mcm10 is in a complex with pol-alpha throughout the cell cycle.

232 The recruitment of pol alpha to chromatin during G1 is independent of pre-R

233 rase delta (Pol delta), which takes over for Pol alpha to complete lagging-strand replication.

234 nes significantly strengthens the ability of pol alpha to identify the resulting 1-deazapurines as wr

235 g to eighty-nucleotide ssDNA, and recruiting pol alpha to Mcm2-7 in vitro.

236 g, helicase assembly, and the recruitment of pol alpha to Mcm2-7.

237 dicate that Ctf4 can couple two molecules of Pol alpha to one CMG helicase within the replisome, prov

238 imer-template species need not interact with pol alpha to regulate further primase activity.

239 recruitment of DNA polymerase alpha-primase (pol alpha) to chromatin.

240 ized DNA, resulting in incorporation of such Pol-alpha tracts and increased mutation rates at specifi

241 pha activity assays revealed the presence of pol alpha transcripts and a sixfold increase in activity

242 proceeds via a Hoogsteen base pair and that pol alpha uses N3 of a purine dNTP to block this incorpo

243 chemical features of purine dNTPs that human pol alpha uses to discriminate between right and wrong d

244 These data indicate that pol alpha uses two orthogonal screens to maximize its fi

245 opposite the abasic lesion, indicating that pol alpha was responsible for bypass.

246 n-complementary deoxynucleotides into DNA by pol alpha was substantially decreased by p53.

247 t that failed to activate or bind to DNA and pol alpha, was not observed in this complex.

248 oding DNA replication activities such as DNA Pol alpha, we now show that the majority of genes encodi

249 ivity and bind to single-stranded DNA and to pol alpha were compared.

250 t repair efficiencies for mismatches made by Pol alpha were consistently higher than for those same m

251 Reactions catalyzed by pol alpha were strongly blocked at a position one base b

252 sical association with DNA polymerase alpha (Pol alpha), which extends the RNA primer with deoxynucle

253 t errors made by yeast DNA polymerase alpha (Pol alpha), which initiates Okazaki fragments during lag

254 Pol delta and Pol alpha, which conduct lagging strand replication, inc

255 lesion; stronger blockage was observed with pol alpha, while with human pol eta or pol kappa, a frac

256 e, we investigate their roles by using yeast pol alpha with a Leu868Met substitution.

257 on proteins, including DNA polymerase alpha (pol alpha), with chromatin.

258 se a handoff mechanism to load and stabilize pol alpha within the replication fork.

259 (CMG) DNA helicase to DNA polymerase alpha (Pol alpha) within the replisome.