ライフサイエンスコーパス: Poleta

1 Poleta acts like a 'molecular splint' to stabilize damag

2 Poleta and polbeta incorporated dGTP opposite oxoA ~170-

3 Poleta discriminates poorly between the correct and inco

4 Poleta displayed "burst" kinetics for nucleotide incorpo

5 Poleta has been shown to be ubiquitinated at one primary

6 Poleta is highly inefficient at inserting a nucleotide o

7 Poleta possesses a ubiquitin-binding zinc finger (ubz) d

8 Poleta truncations lacking these domains fail to correct

9 Poleta-deficient cells exhibited greater numbers of telo

10 - and (-)-trans-anti-BPDE-N2-dG DNA adducts, Poleta, Polzeta and Rev1 together are required for G-->T

11 tation of the D570 residue adversely affects Poleta function.

12 Our studies revealed that, although Poleta contributes to the tolerance of cisplatin adducts

13 Two residues conserved among Poleta orthologues form specific hydrogen bonds with the

14 tspot/coldspot targeting of AID activity and Poleta errors to maximize SHM in the CDRs and minimize m

15 AID and Poleta function during B-cell affinity maturation by cat

16 feature of our system is the use of AID and Poleta to perform repetitive affinity maturation on libr

17 replication of ultraviolet-damaged DNA, and Poleta promotes replication through many other DNA lesio

18 Our results show that both Dpo4 and Poleta incorporate dATP opposite the 5' T of the CPD via

19 ine the mechanisms of CPD bypass by Dpo4 and Poleta using nucleotide analogs that specifically disrup

20 ing opposite an abasic-like intermediate and Poleta using the normal Watson-Crick base pairing.

21 eplicate through distorting DNA lesions, and Poleta synthesizes DNA with a low fidelity.

22 independently of PCNA monoubiquitination and Poleta, whereas RAD18 plus Poleta, REV1, and Polzeta are

23 point response of cells lacking Polkappa and Poleta is not the result of stalled replication forks.

24 ing translesion DNA polymerases Polkappa and Poleta significantly prolonged the checkpoint response,

25 (TLS) by DNA polymerases zeta (Polzeta) and Poleta and postreplicational repair mediated by the Mms2

26 Enzymes such as Rev1 and Poleta may contribute to the insertion of these other nu

27 In vivo, WRN and Poleta colocalize at replication-dependent foci in respo

28 Also, USP7 physically binds Poleta in vitro and in vivo.

29 its need for Watson-Crick hydrogen bonding, Poleta can stabilize the adduct in its active site.

30 Both Poleta and Poldelta insert a C or a T residue opposite f

31 leta (rad30), Rev1, Polzeta (rev3), and both Poleta and Polzeta, translesion synthesis was reduced to

32 Poleta and slowed down the turnover of both Poleta and p53 proteins through destabilizing their E3 l

33 These observations suggest that both Poleta and Polkappa rely on W-C hydrogen bonding for loc

34 the mechanism of nucleotide incorporation by Poleta and show that it utilizes an induced-fit mechanis

35 and accuracy of nucleotide incorporation by Poleta are severely impaired.

36 opposite the 3' T of the (6-4) TT lesion by Poleta, and Polzeta inserts the correct nucleotide A opp

37 a-dependent TLS, but not for TLS mediated by Poleta in yeast cells.

38 at Rev1 is indispensable for TLS mediated by Poleta, Poliota, and Polkappa but is not required for TL

39 incorporation, WRN increases mutagenesis by Poleta.

40 se, Rad18-mediated trans-lesion synthesis by Poleta is dispensable for damage-tolerance in G(1) (beca

41 Thus, we expect DNA synthesis by Poleta to be more accurate than that predicted from the

42 The stimulation of DNA synthesis by Poleta with PCNA or Ub-PCNA was not affected by mutation

43 DNA synthesis by Poleta, a low-fidelity polymerase able to replicate thro

44 Polzeta, error-free translesion synthesis by Poleta, and postreplication repair of discontinuities by

45 ge step after the lesion bypass synthesis by Poleta.

46 gen bonding is required for DNA synthesis by Poleta; in this regard, Poleta differs strikingly from c

47 relative contributions of error-free TLS by Poleta and error-prone TLS by Poltheta to the replicatio

48 ystal structures of Saccharomyces cerevisiae Poleta (also known as RAD30) in ternary complex with a c

49 alytically-defective mutants deubiquitinates Poleta and increases its cellular steady-state level.

50 pendence upon W-C hydrogen bonding than does Poleta.

51 -immunoprecipitate with human and Drosophila Poleta, respectively, from cultured cells.

52 We generated a null mutation in Drosophila Poleta (dPoleta) and found that dPoleta-derived embryos

53 On the basis of the structures, eight Poleta missense mutations causing XPV can be rationalize

54 as largely abolished in cells lacking either Poleta, Polzeta or Rev1.

55 This property enables Poleta to bypass lesions with distorted DNA geometries,

56 ast, which lacks the RAD30 gene that encodes Poleta and the Pol32 subunit of DNA polymerase delta (Po

57 absence of RAD30-encoded DNA polymerase eta (Poleta) but not in the absence of REV3-encoded DNA Polze

58 The yeast RAD30-encoded DNA polymerase eta (Poleta) bypasses a cis-syn thymine-thymine dimer efficie

59 DNA polymerase eta (Poleta) catalyzes the efficient and accurate synthesis o

60 DNA polymerase eta (Poleta) functions in error-free bypass of ultraviolet li

61 DNA polymerase eta (Poleta) functions in error-free replication of UV-damage

62 DNA polymerase eta (Poleta) has the unique ability to replicate through UV-l

63 DNA polymerase eta (Poleta) has unique and pivotal functions in several DNA

64 etic studies on Y-family DNA polymerase eta (Poleta) have suggested that the polymerase undergoes a r

65 ave biochemically shaped DNA polymerase eta (Poleta) in plants, we expressed in Escherichia coli prot

66 ement of yeast and human DNA polymerase eta (Poleta) in the replicative bypass of m6G lesions in DNA.

67 ave examined the role of DNA polymerase eta (Poleta) in translesion synthesis of AP sites by replicat

68 Polymerase eta (Poleta) is a low fidelity translesion synthesis DNA poly

69 DNA polymerase eta (Poleta) is a low-fidelity enzyme able to replicate throu

70 DNA polymerase eta (Poleta) is a unique translesion DNA synthesis (TLS) enzy

71 DNA polymerase eta (Poleta) is unique among eukaryotic DNA polymerases in it

72 DNA polymerase eta (Poleta) is unique among eukaryotic polymerases in its pr

73 tably, cells depleted of DNA polymerase eta (Poleta) or the E3 ubiquitin ligase RAD18 were proficient

74 dine deaminase (AID) and DNA polymerase eta (Poleta) to diversify immunoglobulin variable gene (IgV)

75 itin ligase Rad18 guides DNA Polymerase eta (Poleta) to sites of replication fork stalling and mono-u

76 ligase Rad18 chaperones DNA polymerase eta (Poleta) to sites of UV-induced DNA damage and monoubiqui

77 pecialized repair polymerase polymerase eta (Poleta) to the detergent-resistant chromatin compartment

78 ing DNA replication, and the polymerase eta (Poleta) translesion synthesis DNA polymerase additionall

79 aused by a deficiency in DNA polymerase eta (Poleta), a DNA polymerase that enables replication throu

80 8 is targeted to PCNA by DNA polymerase eta (Poleta), the XPV gene product that is mutated in XPV pat

81 ecent structural data on DNA polymerase eta (Poleta), we elucidate its translocation mechanism, which

82 Eukaryotic cells possess DNA polymerase eta (Poleta), which has the ability to replicate past a cis-s

83 ota's closest paralogue, DNA polymerase eta (Poleta), with which Poliota shares many functional simil

84 thesis (TLS) mediated by DNA polymerase eta (Poleta).

85 es in WA motifs preferred by polymerase-eta (Poleta), and a strand-biased increase in the mutation fr

86 isplatin adducts by the TLS polymerases eta (Poleta), REV1, and zeta (Polzeta) based on the observati

87 Moreover, during RNA extension Poleta performs error-free bypass of the 8-oxoguanine an

88 1 (WRNIP1) in Rev1-dependent TLS by Y family Poleta, Poliota, or Polkappa and show that WRN, WRNIP1,

89 repsilon in vitro, and that the low fidelity Poleta is not accessible to repair synthesis during NER.

90 ogether, these features define the basis for Poleta's action on ultraviolet-damaged DNA that is cruci

91 s an indispensable scaffolding component for Poleta, Poliota, and Polkappa, which function in TLS in

92 Ala substitution at S409 was compromised for Poleta association and did not redistribute Poleta to nu

93 to PCNA through ubiquitin is dispensable for Poleta's function.

94 , USP7 directly serves as a specific DUB for Poleta.

95 interaction is found to be nonessential for Poleta's function.

96 CNA via its PIP domain is a prerequisite for Poleta's ability to function in TLS in human cells and t

97 er with the incoming A has been proposed for Poleta.

98 esults define a novel non-catalytic role for Poleta in promoting PCNA monoubiquitination and provide

99 Our results suggest an additional role for Poleta in the prevention of internal cancers in humans t

100 e whether human Polkappa, which differs from Poleta in having a higher fidelity and which, unlike Pol

101 When the pip motif or ubz domain of a given Poleta binds to the IDCL of PCNA, such interaction becom

102 studies have shown that both yeast and human Poleta are low-fidelity enzymes, and they misincorporate

103 Both Saccharomyces cerevisiae and human Poleta efficiently insert two adenines opposite the two

104 We find that both yeast and human Poleta extend from mismatched base pairs with a frequenc

105 (6-4) TT photoproduct, both yeast and human Poleta preferentially insert a G residue, but they are u

106 ypass of this lesion, and mutations in human Poleta result in the cancer prone syndrome, the variant

107 ently and accurately, and mutations in human Poleta result in the cancer-prone syndrome, the variant

108 the first time a crystal structure of human Poleta (hPoleta) in binary complex with its DNA substrat

109 high-resolution crystal structures of human Poleta at four consecutive steps during DNA synthesis th

110 b-binding zinc finger (UBZ) domains of human Poleta in TLS, we have determined whether the C-terminal

111 b-binding zinc finger (UBZ) domains of human Poleta make to its functional interaction with PCNA, its

112 high-resolution crystal structures of human Poleta with a template AraC residue positioned opposite

113 basis of the low level of fidelity of human Poleta.

114 human Polkappa is 1.7-fold lower than human Poleta, but 33-fold higher than human Polbeta, a DNA pol

115 Surprisingly, however, we find that human Poleta differs from the yeast enzyme in several importan

116 t in Polzeta-dependent UV mutagenesis and in Poleta-dependent TLS, this PCNA mutation inhibits postre

117 nuclear antigen (PCNA) monoubiquitination in Poleta-proficient but not in Poleta-deficient XPV (Xerod

118 iquitination in Poleta-proficient but not in Poleta-deficient XPV (Xeroderma pigmentosum variant) cel

119 ns defective in MMR (Msh2 or Msh6) and/or in Poleta activity.

120 xpressing full-length catalytically-inactive Poleta exhibit increased recruitment of other error-pron

121 lta holoenzyme is refractory to the incoming Poleta.

122 In cells lacking Poleta (rad30), Rev1, Polzeta (rev3), and both Poleta an

123 imately 26-37% in rad30 mutant cells lacking Poleta, but more deficient in rev1 and almost totally de

124 Although the archael Dpo4, which, like Poleta, belongs to the Y family of DNA Pols, can also re

125 insert a C or a T residue opposite from m6G; Poleta, however, is more accurate, as it inserts a C abo

126 NA synthesis, here we examine the ability of Poleta to extend from base mismatches.

127 res provide a novel basis for the ability of Poleta to promote AraC induced mutagenesis in relapsed A

128 The structures reveal that the ability of Poleta to replicate efficiently through the ultraviolet-

129 carry out TLS opposite 1-MeA, the ability of Poleta to replicate through 1-MeA suggests that despite

130 re only marginally reduced in the absence of Poleta (rad30 mutant).

131 r transcription inhibition as the absence of Poleta.

132 roduct is achieved by the combined action of Poleta and Polzeta, wherein Poleta inserts a nucleotide

133 ggest that the new RNA synthetic activity of Poleta can have in vivo relevance.

134 ify a new specific RNA extension activity of Poleta of Saccharomyces cerevisiae.

135 nce alignments, we identify three classes of Poleta among different species based on the presence or

136 primer termini, the ensuing dissociation of Poleta from DNA may favor the excision of mismatched nuc

137 The C-terminal domain of Poleta binds to both Rad18 and PCNA and promotes PCNA mo

138 As per the current notion, the ubz domain of Poleta binds to the ubiquitin moiety of the ubiquitinate

139 nal analyses, we show that the ubz domain of Poleta, which intrinsically lacks the pip motif directly

140 r antigen (PCNA), facilitating engagement of Poleta with stalled replication forks and promoting tran

141 Such a remarkably high in vivo fidelity of Poleta could not have been anticipated in view of its lo

142 CNA is essential for the in vivo function of Poleta.

143 utane pyrimidine dimers, and inactivation of Poleta (also known as POLH) in humans causes the variant

144 Inactivation of Poleta could afford a useful strategy for enhancing the

145 DNA lesions, and mutational inactivation of Poleta in humans causes the cancer prone syndrome, the v

146 utane pyrimidine dimers, and inactivation of Poleta in humans causes the cancer-prone syndrome, the v

147 of several genes is affected by the lack of Poleta, and that Poleta is enriched over actively transc

148 of USP7 increased the steady-state level of Poleta and slowed down the turnover of both Poleta and p

149 ment and virtually abolished localization of Poleta to nuclear repair foci, both hallmarks of TLS.

150 A replication or damage bypass properties of Poleta.

151 n DDK and is necessary for redistribution of Poleta to sites of replication fork stalling.

152 c protease 7 (USP7), as a novel regulator of Poleta stability.

153 To better understand the role of Poleta in error-free translesion DNA synthesis, here we

154 res also provide an insight into the role of Poleta in replicating through D loop and DNA fragile sit

155 zeta implicates a highly error-free role of Poleta in TLS opposite CPDs in mammalian cells.

156 cells, and suggest that an important role of Poleta is to catalyze extension following A insertion op

157 ccur via an enzyme motion where the shift of Poleta is asynchronous along the two DNA strands.

158 to having a pivotal role in the targeting of Poleta to the replication machinery stalled at DNA lesio

159 We observed enhanced ubiquitylation of Poleta by TRIP and NOPO E3 ligases in human cells and Dr

160 biquitination and Poleta, whereas RAD18 plus Poleta, REV1, and Polzeta are all necessary for replicat

161 DNA polymerase eta (PolH, Poleta) belongs to the Y-family of DNA polymerases and m

162 Here, we show that although Poliota, Poleta, and Polkappa are all able to form a covalent Sch

163 The human Y-family DNA polymerases, Poliota, Poleta, and Polkappa, function in promoting replication

164 al interaction between WRN and the TLS Pols, Poleta, Polkappa, and Poliota.

165 oltheta(-/-), Poleta(-/-), and Poltheta(-/-) Poleta(-/-) mice.

166 and is further exacerbated in Poltheta(-/-) Poleta(-/-) mice compared with Poleta(-/-) mice support

167 of UV-induced skin cancers in Poltheta(-/-), Poleta(-/-), and Poltheta(-/-) Poleta(-/-) mice.

168 accumulation of the low-fidelity polymerase Poleta that also colocalized with PCNA.

169 ene, we show that both the repair polymerase Poleta and the multifunctional factor MRE11/RAD50/NBS1 l

170 y translesion DNA synthesis (TLS) polymerase Poleta is proficient, inserting both correct and incorre

171 bling the error-prone translesion polymerase Poleta activity, and observe an activation-induced deami

172 tional absence of the translesion polymerase Poleta.

173 0 of S. cerevisiae encodes a DNA polymerase, Poleta, that efficiently replicates DNA containing a cis

174 romyces cerevisiae encodes a DNA polymerase, Poleta.

175 Humans have three DNA polymerases, Poleta, Polkappa, and Poliota, which are able to promote

176 translesion DNA synthesis (TLS) polymerases: Poleta, REV1, and Polzeta.

177 en Polzeta(+/-) Poleta(-/-) and Polzeta(+/+) Poleta(-/-) clones.

178 Poleta(-/-) cells compared with Polzeta(+/+) Poleta(-/-) cells, suggesting that pol zeta generates ta

179 rmutation was unaltered between Polzeta(+/-) Poleta(-/-) and Polzeta(+/+) Poleta(-/-) clones.

180 em double-base substitutions in Polzeta(+/-) Poleta(-/-) cells compared with Polzeta(+/+) Poleta(-/-)

181 mismatch repair, by DNA polymerases Polzeta, Poleta, and Pol32, but result from errors made by Poldel

182 distribute Poleta to nuclear foci or promote Poleta-PCNA interaction efficiently relative to wild-typ

183 S1 localize to lambda(R), and that lambda(R)/Poleta colocalizations occur predominately in G(1) phase

184 Poleta association and did not redistribute Poleta to nuclear foci or promote Poleta-PCNA interactio

185 for DNA synthesis by Poleta; in this regard, Poleta differs strikingly from classical high-fidelity D

186 connecting loop (IDCL) of PCNA and regulates Poleta's TLS activity.

187 USP7 regulates Poleta stability through both indirect and direct mechan

188 is at a wide spectrum of dipyrimidine sites, Poleta plays a pivotal role in minimizing the incidence

189 e of NPM1 in DNA damage repair, specifically Poleta-mediated translesion synthesis, base excision, an

190 duced PCNA monoubiquitination by stabilizing Poleta.

191 Here, we test Poleta for its ability to bypass a (6-4) TT lesion which

192 hrough a CPD, it is much less efficient than Poleta.

193 is affected by the lack of Poleta, and that Poleta is enriched over actively transcribed regions.

194 The results clearly demonstrate that Poleta can function independently of the MMR system to p

195 sions, our biochemical studies indicate that Poleta is much more efficient in replicating through m6G

196 air following exposure to IR indicating that Poleta-dependent lesion bypass or RAD18-dependent monoub

197 We show that Poleta can accommodate local perturbation caused by the

198 We show that Poleta is able to extend RNA primers in the presence of

199 These results show that Poleta is involved in translesion synthesis of AP sites

200 It has been suggested that Poleta limits GO-associated mutagenesis exclusively thro

201 yme that operate in a coordinated way at the Poleta.DNA interface.

202 Furthermore, the Poleta-dependent bypass of GO lesions is more efficient

203 In the Poleta pathway, this Pol alone would function at both th

204 e-limiting conformational change step in the Poleta replication cycle likely corresponds to a rate-li

205 A serine cluster in the Poleta-binding motif of Rad 18 is phosphorylated by DDK.

206 We show here that Ser-409 residing in the Poleta-binding motif of Rad18 is phosphorylated in a che

207 The role of the Poleta pip motif in PCNA interaction required for DNA po

208 to the lack of structural information on the Poleta binary complex.

209 and a truncated version containing only the Poleta domain.

210 Furthermore, we showed that the Poleta C-terminal PCNA-interacting protein motif is requ

211 n the NH(2) terminus is highly homologous to Poleta, and the COOH terminus is highly homologous to th

212 CNA monoubiquitination, a function unique to Poleta among Y-family TLS polymerases and dissociable fr

213 ted stress-tolerance pathways by fine-tuning Poleta turnover.

214 ent a model in which TRIP/NOPO ubiquitylates Poleta to positively regulate its activity in translesio

215 Unlike Poleta, another member of this family, which carries out

216 n having a higher fidelity and which, unlike Poleta, is inhibited at inserting nucleotides opposite D

217 d by three different pathways dependent upon Poleta, Poliota, and Polnu, respectively; and that TLS b

218 either by pip motif or ubz domain in various Poleta homologs.

219 tremely sensitive to all four drugs, whereas Poleta depletion had little effect.

220 replicative DNA polymerases (Pols), whereas Poleta promotes proficient and error-free replication th

221 mbined action of Poleta and Polzeta, wherein Poleta inserts a nucleotide opposite the 3' T of the les

222 Poltheta(-/-) Poleta(-/-) mice compared with Poleta(-/-) mice support the conclusion that error-prone

223 The possible role of Ctf7 fusion with Poleta in the replication of Cohesin-bound DNA sequences

224 ge of Saccharomyces cerevisiae Poldelta with Poleta requires both the stalling of the holoenzyme and

225 Efficient association of Rad18 with Poleta is dependent on DDK and is necessary for redistri

226 nd an identical nondamaged sequence by yeast Poleta.

227 udies presented here reveal a role for yeast Poleta in the error-free bypass of cyclobutane dimers an

228 Pre-steady-state kinetic studies of yeast Poleta have indicated that the low level of fidelity of

229 physical and functional interaction of yeast Poleta with proliferating cell nuclear antigen (PCNA) an

230 pha-helix portion of the UBZ domain of yeast Poleta.

231 Purified yeast Poleta performed extension synthesis from the primer 3'

232 ast Polvarepsilon, but not by purified yeast Poleta.