ライフサイエンスコーパス: XPD

1 XPD has a 5' to 3' polarity and the helicase activity is

2 XPD in contrast is shown to be a rigid protein with almo

3 XPD is a 5' to 3' helicase with an essential iron-sulfur

4 XPD was not stalled by substrates containing extrahelica

5 XPD was subsequently recruited to the triplex-induced do

6 XPD, a 5'-3' helicase involved in nucleotide excision re

7 oteins RPA1 and RPA2 differentially affected XPD translocation.

8 phoblastoid cell lines (LCLs), but not in an XPD heterozygote LCL, after exposure to doxorubicin, a D

9 UvrB as a template for the development of an XPD model was tested by mimicking human disease-causing

10 ative helicases: PcrA from superfamily 1 and XPD from superfamily 2.

11 ppressed human osteosarcoma (U2OS) cells and XPD-deficient human fibroblasts.

12 e nucleotide excision repair genes ERCC1 and XPD (Ercc1(d/-) and Xpd(TTD) mice), we explored age-depe

13 human TFIIH complex proteins XPB (ERCC3) and XPD (ERCC2) play a principal role in the degradation of

14 or alleles in DNA repair genes XPF/ERCC4 and XPD/ERCC2 were associated with altered risk for pancreat

15 in the FeS domain of human Bach1 (FancJ) and XPD helicases that result in distinct disease phenotypes

16 HRTEM and XPD simulations show that stacking faults do occur, but

17 5, bcl-2 and bax were observed in normal and XPD LCLs after treatment with doxorubicin, indicating th

18 n-adducted oligonucleotide was observed, and XPD helicase activity was readily inhibited by both sing

19 ithin preincision complexes, it is RPA32 and XPD that are in close contact with the lesion.

20 scopy analyses, we demonstrate that UvrB and XPD are able to load onto DNA and pursue lesion verifica

21 ved to be achieved by the helicases UvrB and XPD in the prokaryotic and eukaryotic processes, respect

22 Both XBP and XPD cells were deficient in repair of nontranscribed DNA

23 , and that gene complementation with XPA and XPD increases resistance to cisplatin.

24 ypothesized that TFIIH DNA helicases XPB and XPD are members of the p53-mediated apoptotic pathway.

25 tailed structures of its constituent XPB and XPD ATPases, and how the core and kinase subcomplexes of

26 of CSB, CSA, or the TFIIH helicases XPB and XPD can also cause defective TCR and CS.

27 iption factor IIH complex, including XPB and XPD helicases involved in promoter melting and open comp

28 cate the nuclear DNA repair proteins XPB and XPD in a cellular defense against retroviral infection.

29 Pase and helicase activities of both XPB and XPD in Core7 to promote NER, whereas non-genuine NER sub

30 DNA repair-deficient XPB and XPD mutant cell lines exhibited an increase in transduct

31 grated provirus, and 2LTR circles in XPB and XPD mutant cells.

32 Here, XPB and XPD mutations are shown to block transcription activatio

33 The XPB and XPD proteins are subunits of RNA polymerase II (RNAP II)

34 -damaged sites; (iii) recruitment of XPB and XPD proteins to UV DNA damage sites; and (iv) increased

35 least two of the subunits of TFIIH (XPB and XPD proteins) are implicated in the disease xeroderma pi

36 s share high homology with the human XPB and XPD proteins.

37 osum complementation groups B and D (XPB and XPD) which are partially defective in the ERCC2 (XPD) an

38 TFIIH DNA helicases, XPB and XPD, are also components in this apoptotic pathway.

39 The DNA helicases XPB and XPD, components of transcription factor TFIIH, have been

40 sms in 3 DNA repair genes: XRCC1, XRCC3, and XPD.

41 Archaeal XPD is closely related in sequence to the eukaryal enzym

42 iochemical studies of the monomeric archaeal XPD homologues have aided a mechanistic understanding of

43 nt with a role in NER, we show that archaeal XPD can initiate unwinding from a DNA bubble structure,

44 g by the iron-sulfur cluster of the archaeal XPD (Rad3) helicase was used as a calibrated proximity s

45 issue, Honda et al. report that the archaeal XPD helicase can bypass a single-stranded DNA-binding pr

46 Here, DNA binding by the archaeal XPD helicase from Thermoplasma acidophilum has been inve

47 ren treated for de novo AML was performed at XPD exon 23.

48 evidence for DNA-mediated signaling between XPD and Endonuclease III (EndoIII), a base excision repa

49 repair of mtDNA was markedly reduced in both XPD-suppressed human osteosarcoma (U2OS) cells and XPD-d

50 though iron-sulfur (Fe-S) cluster binding by XPD is required for activity, the process mediating Fe-S

51 lectrodes, we show DNA-mediated signaling by XPD, a helicase that contains a [4Fe-4S] cluster and is

52 bp) resolution, we analyzed DNA unwinding by XPD helicase, a Superfamily 2 (SF2) DNA helicase involve

53 entosum complementation group B (XPB) and D (XPD) genes and a cyclin-dependent protein kinase encoded

54 Xeroderma pigmentosum factor D (XPD) is a 5'-3' superfamily 2 helicase and the founding

55 on 751 of the xeroderma pigmentosum group D (XPD) DNA repair gene were significantly more likely to h

56 The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase that functions in nucle

57 The xeroderma pigmentosum group D (XPD) helicase is a component of the transcription factor

58 Xeroderma pigmentosum group D (XPD) helicase is a component of the transcription factor

59 The xeroderma pigmentosum group D (XPD) helicase is a subunit of transcription/DNA repair f

60 The xeroderma pigmentosum group D (XPD) protein is a subunit of transcription factor TFIIH

61 The Xeroderma pigmentosum group D (XPD) protein is an essential participant in nucleotide e

62 repair gene, Xeroderma pigmentosum group D (XPD), modified the risk.

63 patients, the xeroderma pigmentosum group D (XPD)-751, x-ray cross-complementing group 3 (XRCC3) and

64 Xeroderma pigmentosum group D (XPD/ERCC2) encodes an ATP-dependent helicase that plays

65 ng high-resolution X-ray powder diffraction (XPD) and rotation electron diffraction (RED) techniques.

66 By combining X-ray powder diffraction (XPD), high-resolution transmission electron microscopy (

67 Apart from two canonical helicase domains, XPD is composed of a 4Fe-S cluster domain involved in DN

68 h XPD-ssDNA binding but markedly slowed down XPD translocation.

69 In contrast, cells lacking either XPD, the 3'-helicase, or the 3'-endonuclease XPG were eq

70 Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorte

71 ree nucleotide excision repair genes (ERCC1, XPD, and XPF), a gene involved in double-strand break re

72 ncies for 16 SNPs in DNA repair genes ERCC1, XPD/ERCC2, XPC, XPF/ERCC4, OGG1, and XRCC1 were compared

73 isplatin treatment, including: c-jun, ERCC1, XPD and XRCC1.

74 nd/or protein levels included: c-jun, ERCC1, XPD, XRCC1, Gli1, Gli2, SHH, IHH, GAPDH and alpha-tubuli

75 tion of three genes essential to NER (ERCC1, XPD) and base excision repair (XRCC1).

76 Gli1, c-jun, and the upregulation of ERCC1, XPD and XRCC1 in cisplatin-resistant human ovarian cance

77 isms in DNA repair genes APE1, XRCC1, ERCC1, XPD, and XRCC3 in predicting therapeutic outcomes of old

78 to complement extracts prepared from ERCC2 (XPD)- and ERCC3 (XPB)-deficient cells, respectively, in

79 but is devoid of detectable levels of ERCC2 (XPD) and CAK.

80 which are partially defective in the ERCC2 (XPD) and ERCC3 (XPB) helicase activities shared between

81 yclin H, and p36/MAT1) as well as the ERCC2 (XPD) protein.

82 d to the DRC phenotype were defined in ERCC2/XPD, PHACTR2, and DUSP1.

83 We therefore examined XPD polymorphisms at Lys751Gln and Asp312Asn in 341 whit

84 Moreover, the TFIIH factor, XPD, occupies a central role in triggering apoptosis in

85 First, XPD was found to associate in a mutually exclusive fashi

86 re carriers of at least one minor allele for XPD/ERCC2 at D312N (OR, 2.78; 95% CI, 1.28-6.04) or D711

87 nd XPC bind damaged DNA and are required for XPD cross-linking to the psoralen-adducted base, neither

88 match, which is not a specific substrate for XPD but, like a lesion, inhibits CT.

89 as well as the polymorphic DNA repair genes XPD and XRCC1, in influencing response to chemotherapy a

90 mutations in DNA repair/transcription genes XPD, XPB or TTDA, and in TTDN1, a gene of unknown functi

91 mental and physical developmental delay, has XPD mutations not previously reported, and barely detect

92 It has been proposed that the 5'-3' helicase XPD (xeroderma pigmentosum group D) protein plays a deci

93 nit of the TFIIH complex, the 5'-3' helicase XPD, has been identified in archaea.

94 but not expression of the 5' --> 3' helicase XPD.

95 The archaeal Rad3 helicase XPD (xeroderma pigmentosum group D protein) from Ferropl

96 harbor mutations in the TFIIH DNA helicases XPD or XPB.

97 with the localization of the TFIIH helicases XPD and XPB, support a DNA translocation model of XPB an

98 PARP cleavage was not delayed in XPD LCLs in response to anti-Fas (CD95) antibody-mediate

99 terface between the Arch and 4FeS domains in XPD.

100 Similar to the findings in XPD-deficient cells, mitochondrial common deletion and o

101 lar matrix (ECM), in TTD patients mutated in XPD compared with their healthy parents.

102 tanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

103 Mutations in XPD helicase, required for nucleotide excision repair (N

104 Mutations in XPD that affect DNA repair but not transcription result

105 Here we show that the specific mutations in XPD that cause TTD result in reduced expression of the b

106 Genetic polymorphisms in XPD and XRCC1 may be important prognostic factors in pla

107 Polymorphisms in XPD, a member of the nucleotide excision repair pathway,

108 st restore helicase activity to the inactive XPD(T46I) protein.

109 d in a number of DNA repair genes, including XPD, but the effect of these polymorphisms on DNA repair

110 f extramitochondrial Fe-S proteins including XPD.

111 es important for genomic stability including XPD (nucleotide excision repair), DDX11 (sister chromati

112 show that triplexes are capable of inducing XPD-independent double strand breaks, which result in th

113 t, a 5' --> 3' DNA helicase catalyzed by its XPD subunit, and a carboxyl-terminal domain (CTD) kinase

114 The XPD(R658H) TTD protein, like XPD(T46I/R658H), is codominant when overexpressed in V-H

115 eukaryotic helicases that includes mammalian XPD, an enzyme involved in transcription-coupled nucleot

116 We show that monomeric XPD unwinds duplex DNA in 1-bp steps, yet exhibits frequ

117 y mimicking human disease-causing mutations (XPD: R112H, D234N, R601L) in UvrB (E110R, D338N, R506A)

118 pair of nuclear DNA, however, whether or not XPD exerts similar functions in mitochondria remains elu

119 t also impairs the DNA unwinding activity of XPD and the nucleotide excision repair activity of TFIIH

120 ation in the Walker A box in both alleles of XPD and lacks DNA helicase activity.

121 ion studies indicate that the association of XPD with the CIA targeting complex occurs in the cytopla

122 Quantifying the sequence dependence of XPD stepping dynamics with near base pair resolution, we

123 her, our results identify the ARCH domain of XPD as a platform for the recruitment of CAK and as a po

124 in understanding the molecular mechanism of XPD human disease causing mutations.

125 found to stimulate the signaling pathway of XPD-dependent apoptosis.

126 ive stress showed an enhanced recruitment of XPD into mitochondrial compartment.

127 FM studies, we observe the redistribution of XPD onto kilobase DNA strands containing a single base m

128 A crystal structure of XPD from Sulfolobus acidocaldiarius that lacks helicase

129 The 2.25 A crystal structure of XPD from the crenarchaeon Sulfolobus tokodaii, presented

130 ential assembly process for Fe-S assembly on XPD and highlight the existence of quality control mecha

131 Second, disrupting Fe-S cluster assembly on XPD by either 1) depleting cellular iron levels or 2) ut

132 Individually, only XPD Asp312Asn, RAG1 Lys820Arg, and a p53 intronic SNP ex

133 ase subunits xeroderma pigmentosum (XP) B or XPD yield overlapping DNA repair and transcription syndr

134 an cells deficient in FANCJ but not DDX11 or XPD.

135 V cDNA appeared more stable in mutant XPB or XPD cells.

136 rescued by transferring the wild-type XPB or XPD gene into the corresponding mutant cells.

137 r and have germ-line mutations in the XPB or XPD gene, but not in the XPA or XPC gene, have a deficie

138 virus viral production was greater in XPB or XPD mutant cells but not XPA mutant cells.

139 TFIIH from cells with XPB or XPD mutations was defective in supporting repair, wherea

140 of apoptotic levels in cells from WS, XPB or XPD patients was attained only by overexpression of the

141 formation and find that mutations in XPB or XPD, the DNA helicase subunits of the transcription and

142 Expressed wild-type XPC or XPD cDNAs in these cells restored the survival to UVC ra

143 ng blocks Fe-S cluster assembly and prevents XPD incorporation into TFIIH.

144 Rad3 (xeroderma pigmentosum group D protein (XPD)) helicase is a prototypical member of the Rad3 fami

145 he human nucleotide excision repair protein, XPD, was developed based on the structural and functiona

146 ein levels of the core TFIIH component Rad3 (XPD homologue) and Ssl2 (XPB homologue) were significant

147 lyzed the substrate specificity of the Rad3 (XPD) helicase from Ferroplasma acidarmanus (FacRad3) and

148 d by mutating two highly conserved residues (XPD, His-237 and Asp-609; UvrB, H341A and D510A).

149 uence similarity to the human (Homo sapiens) XPD and yeast (Saccharomyces cerevisiae) RAD3 genes requ

150 previously suggested links between specific XPD mutations in the fetal genome and the risk of placen

151 ctly interacts with the DNA helicase subunit XPD/Rad3 in native TFIIH and is required for the integri

152 ponent of transcription factor II H (TFIIH), XPD is involved in DNA unwinding during nucleotide excis

153 We conclude that XPD Lys751Gln polymorphism may be an important marker in

154 Our findings clearly demonstrate that XPD plays crucial role(s) in protecting mitochondrial ge

155 is study, we provide the first evidence that XPD is localized in the inner membrane of mitochondria,

156 ovide further support to the hypothesis that XPD and p53 can functionally interact in a p53-mediated

157 We hypothesized that XPD Lys751Gln polymorphism may play a role in causation

158 the only data in pediatric AML, suggest that XPD genotype does not affect the etiology or outcome of

159 e microscopy reveals for the first time that XPD utilizes different recognition strategies to verify

160 The XPD helicase (Rad3 in Saccharomyces cerevisiae) is a com

161 The XPD structural model can be employed in understanding th

162 The XPD(R658H) TTD protein, like XPD(T46I/R658H), is codomin

163 NA: these proteins are RPA70, RPA32, and the XPD subunit of TFIIH.

164 erface between the p62 Anchor region and the XPD subunit.

165 We have cloned the XPD variants Lys751Gln, Asp312Asn, and Lys751Gln-Asp312A

166 strate the role of CAK in downregulating the XPD helicase activity within TFIIH.

167 s with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mut

168 Furthermore, homozygosity for the XPD codon 751 glutamine variant was associated with a si

169 and space group symmetry were found from the XPD data, and were essential for the initial analysis of

170 Furthermore, the XPD Lys751Gln polymorphism was a significant modifier of

171 ession analysis, the Gln/Gln genotype in the XPD codon 751 showed the strongest association with both

172 patients with characterized mutations in the XPD gene have the haematological features of beta-thalas

173 studies have identified polymorphisms in the XPD gene that are associated with increased risk of brai

174 complex disorder caused by mutations in the XPD gene which affect both DNA repair and transcription.

175 s of genotype-phenotype relationships in the XPD gene.

176 Mutations in the XPD helicase component of TFIIH can result in the divers

177 Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH

178 Specific mutations in the XPD subunit of transcription factor IIH result in combin

179 ism to evaluate genetic polymorphisms of the XPD (Asp312Asn) and XRCC1 (Arg399Gln) DNA repair genes i

180 ses, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and me

181 dence that three common polymorphisms of the XPD gene (C156A, Asp312Asn, and Lys751Gln) may be associ

182 Here we report the first involvement of the XPD gene in a new case of UV-sensitive COFS syndrome, wi

183 The polymorphisms C156A and Asp312Asn of the XPD gene were not associated with response to 5-fluorour

184 nd no differences in the distribution of the XPD Lys751Gln or XRCC1 Arg194Trp genotypes.

185 sate for the T46I mutation by perturbing the XPD structure in a way that counteracts the effect of th

186 These data suggest that the XPD codon 751 glutamine variant protects against myeloid

187 927 patients with AML, we show here that the XPD codon 751 glutamine-encoding variant significantly a

188 The value of this XPD model demonstrates the generalized approach for the

189 , group D (XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln).

190 at apoptosis is reduced and delayed in three XPD lymphoblastoid cell lines (LCLs), but not in an XPD

191 repaired by NER may not present a barrier to XPD translocation in vivo, in contrast to some predictio

192 XPC and TTD/XPD cell lines were complemented using retroviral transf

193 repair rate, in the complemented XPC and TTD/XPD cells, almost all of the CPDs at "hotspots" for muta

194 In both XPC and TTD/XPD complemented lines, CPD repair on the non-transcribe

195 These results suggest that the two XPD polymorphisms have a modulating effect on DRC, espec

196 Here, we use XPD as a prototypical Fe-S protein to further characteri

197 pleting cellular iron levels or 2) utilizing XPD mutants defective in either Fe-S cluster or CIA targ

198 other toxicities were also found for variant XPD genotypes/haplotypes.

199 When XPD and EndoIII are mixed together, they coordinate in r

200 Whereas XPD does not share significant sequence identity with Uv

201 ent study puts to rest the debate of whether XPD helicase 'verifies' the appropriateness of the DNA d

202 rocess occurs in a stepwise fashion in which XPD acquires a Fe-S cluster from the CIA targeting compl

203 RPA1 competed with XPD for ssDNA access.

204 as detected to be physically interacted with XPD.

205 In contrast, RPA2 did not interfere with XPD-ssDNA binding but markedly slowed down XPD transloca

206 Patients with XPD Gln751C/Asp312G ('D') haplotype were more likely to

207 used to identify interacting factor(s) with XPD and TUFM, a mitochondrial Tu translation elongation

208 Gene activation was undiminished in XPA, XPD and XPG human cell lines, indicating that activation

209 m cells deficient in the NER genes XPG, XPA, XPD or XPF were resistant to Et743, and sensitivity was

210 e nucleotide excision repair apparatus (XPB, XPD, XPG and CSB), cells defective for the ERCC1-XPF str

211 en-subunit TFIIH core complex formed by XPB, XPD, p62, p52, p44, p34, and p8 is competent for DNA rep

212 xploited the availability of the cloned XPB, XPD, p62, p44, and p34 genes (all of which encode polype

213 r is TFIIH, which has a 6-subunit core (XPB, XPD, p44, p34, p52, p62) and a 3-subunit kinase (CAK).

214 DNA helicase superfamily that includes XPB, XPD, and BLM.

215 Mutations in the TFIIH subunits XPB, XPD, and p8 lead to severe premature ageing and cancer p

216 Defects in the XPB, XPD, and XPG genes can result in three different syndrom

217 with CS symptoms have mutations in the XPB, XPD, or XPG genes, which result in UV hypersensitivity a

218 Our analyses demonstrate that the XPB, XPD, p44, and p62 proteins interact with each other.

219 nducted a similar analysis in XPA, XPB, XPC, XPD, and CSB fibroblasts.