ライフサイエンスコーパス: BER

1 BER counters the mutagenic and cytotoxic effects of dama

2 BER gene expression levels and IFN treatment responses w

3 BER genes NEIL3 was down-regulated in IFN-treated patien

4 BER genes were assessed by quantitative RT-PCR.

5 ant, AID(S38A), cannot interact with APE1, a BER protein.

6 n oxidized dNTPs pool together with aberrant BER processing contribute to TNR expansion in non-replic

7 led to provide excision of the 5'-adenylated BER intermediate in mitochondrial extracts.

8 Therefore, although BER of simple lesions occurs rapidly, pathway choice and

9 We conclude that multiple interactions among BER proteins lead to large complexes, which are critical

10 APOBEC3 and BER gene expression at treatment endpoints partially cor

11 otes the polymerase activity of Pol-beta and BER efficiency but also enhances the classic NHEJ repair

12 results provide direct evidence that MMR and BER, operating together, form a novel hybrid pathway tha

13 general sensor of DNA damage in both NER and BER pathways, facilitating damage recognition in the con

14 ads to concurrent relocalization of NPM1 and BER components from nucleoli to the nucleoplasm, and cel

15 l mechanistic switch between replication and BER.

16 Here we show that NPM1 stimulates APE1 BER activity in cells.

17 This attempted BER accounts for many of the potentially lethal or mutag

18 Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-beta an

19 Gh lesions are excellent substrates of both BER and NER.

20 cient in repair of endogenous DNA lesions by BER.

21 CC1 and PARP1 is revealed to be modulated by BER intermediates to different extents, depending on the

22 t nucleosomes control the patch size used by BER.

23 portant contributors in controlling cellular BER protein levels, enzymatic activities, protein-protei

24 itro Subsequent restoration of the chaperone-BER complex in cell, presumably after completion of repa

25 BER product ratios may depend on competitive BER and NER protein binding to these lesions.

26 lacking the CTD, not only inhibits complete BER in vitro but also prevents its chromatin association

27 zed base and a ribonucleotide can compromise BER and RER in repeated sequences.

28 ocessing of the 5'-adenylated dRP-containing BER intermediate.

29 In contrast, BER activity is affected by the presence of a ribonucleo

30 r of the whole BER pathway by 1) controlling BER protein levels, 2) regulating total BER capacity, an

31 PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosyl

32 displayed reduced expression of several core BER enzymes (PARP1, LIG3 and POLbeta).

33 ow that the LigC complex interacts with core BER enzymes in vivo and demonstrate that together these

34 ngs on NEIL2's role in transcription-coupled BER.

35 (i) regulating the expression of a critical BER enzyme (Mag1), (ii) supporting efficient DNA damage

36 le selectively knocking out or down critical BER proteins to identify the impact on luciferase expres

37 more, GAPDH knockdown dramatically decreases BER efficiency and sensitizes cells to DNA damaging agen

38 The levels of the detected BER intermediates are 1 and 2 orders of magnitude lower

39 viously unidentified role of OGG1-driven DNA BER in the generation of endogenous signals for inflamma

40 During BER of naked DNA substrates, APE1 completely bypasses th

41 During BER of oxidized bases in naked DNA, products generated b

42 e of its slow polymerization activity during BER in vivo.

43 referentially lead to repeat deletion during BER by disrupting the balance between the addition and r

44 ion forks collide with SSBs generated during BER.

45 ease responsible for the DNA incision during BER.

46 nd stimulatory effect on DNA ligation during BER in a hairpin loop.

47 We demonstrate that during BER of 8-oxoguanine (8-oxodG) in TNR sequences, DNA poly

48 ator are further crucial to ensure efficient BER, by promoting AAG and APE1 chromatin recruitment.

49 complexes, which are critical for efficient BER in mammalian cells, and the CTD interaction could be

50 e been preserved during evolution to enhance BER in chromatin.

51 y, using biochemical approaches, we examined BER enzymatic activities and their influence on TNR R-lo

52 In summary, in human cell extracts, BER and NER activities co-exist and excise Gh and Sp DNA

53 t H2AX ADP-ribosylation not only facilitates BER repair, but also suppresses the gammaH2AX-mediated D

54 fidence interval [CI], .22-.70) and a faster BER from the TTP model (OR, 0.71; 95% CI, .55-.94).

55 In the case of mouse embryonic fibroblasts, BER of the Sp lesion is strongly reduced in NEIL1(-/-) r

56 3 glycosylase to the sites of DNA damage for BER.

57 te towards the 3'end in regions enriched for BER enzymes AAG and APE1, Elongator and active RNA pol I

58 BER pathway, our data suggest a function for BER proteins in the regulation of ribogenesis.

59 iation and that has broader implications for BER as a whole.

60 herein the activity of several enzymes [four BER-initiating DNA glycosylases and the downstream proce

61 he oxidatively modified DNA base OG to guide BER activity in a gene promoter and impact cellular phen

62 recent advances in the understanding of how BER mediates this critical component of epigenetic regul

63 studied on naked DNA, it remains unclear how BER efficiently operates on chromatin.

64 However, it remains unknown how BER in R-loops can mediate TNR instability.

65 However, BER also performs essential functions in processes other

66 In the past several years, however, BER was found to play additional roles in genome mainten

67 The present study aimed to examine if BER activity of OGG1 is required for pro-inflammatory ge

68 hypoxia with consequences including impaired BER and down regulation of the ATMIN transcriptional tar

69 w key regulation point for pathway choice in BER.

70 epair of these lesions, and as deficiency in BER activity results in DNA damage it has been proposed

71 1 mutation frequencies in yeast deficient in BER endonucleases or DNA damage tolerance proteins.

72 olely responsible for the deglycosylation in BER enzymes, however our results suggest an alternative

73 ed these reporters to measure differences in BER capacity across a panel of cell lines collected from

74 se) glycohydrolase (PARG) are key enzymes in BER that elongate and degrade PAR polymers on target pro

75 A factor of more than 100 improvement in BER was demonstrated within the laboratory and approxima

76 S229L participates in BER, but due to its lower catalytic rate, does so more s

77 strand (NTS) of yeast genes, particularly in BER-deficient strains, due to higher damage formation on

78 t Rev1 could serve as a backup polymerase in BER and could potentially contribute to AID-initiated an

79 beta and there is a significant reduction in BER polymerase extension beyond 1 nt, creating a strikin

80 thus has an indirect but significant role in BER in vivo that may also be important for NPM1c+ tumori

81 zymes that catalyze the first three steps in BER can act at many sites in nucleosomes without the aid

82 ediates generated during successive steps in BER may prove mutagenic or lethal, making it critical th

83 PD-L1 upregulation in BER-depleted cells requires ATR/Chk1 kinase activities,

84 s within nucleosomes significantly influence BER efficiency; moreover, this effect is asymmetric rela

85 Our findings show that AAG-initiated BER at alkylated DNA bases induces sex-dependent RD prim

86 ate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a n

87 espite its role in DNA repair, AAG-initiated BER promotes cytotoxicity in a process dependent on poly

88 increase repair fidelity of MUTYH-initiated BER.

89 t pre-excision step(s) during OGG1 initiated BER evoked by ROS facilitates NF-kappaB DNA occupancy an

90 ities enabling suppression of OGG1-initiated BER and coordination of TDG-initiated BER at this tandem

91 tiated BER and coordination of TDG-initiated BER at this tandem alteration in the CpG dinucleotide.

92 The overall TDG-initiated BER of the Tp8-oxoG dinucleotide is significantly reduce

93 Furthermore, in TDG-initiated BER, TDG remains bound to its product AP site blocking O

94 emethylation process involving TDG-initiated BER.

95 mine DNA glycosylase (hTDG), which initiates BER of mutagenic and cytotoxic G:T and G:U mispairs in D

96 Interestingly, BER/SSBR inhibition suppressed gene activation.

97 into the complex role of SUMOylation of key BER proteins during active DNA demethylation-a role they

98 available data on characterized PTMs of key BER proteins, the functional consequences of these modif

99 and break repair (SSBR) and tumours with low BER/SSBR gene expression show high microsatellite instab

100 limited because most methods used to measure BER activity are cumbersome, time consuming and, for the

101 Measuring BER capacity in living cells is valuable for both basic

102 Rev1 and demonstrated the enzyme can mediate BER in vitro The full-length Rev1 protein and its cataly

103 ar metabolism in the absence of AAG-mediated BER initiation is unclear.

104 d Rip3 The activity of PARP1, which mediates BER, cell death, and inflammation, was increased in PR c

105 Interaction between mitochondrial BER enzymes was significantly affected in the presence o

106 of hEXOG suggest a pathway for mitochondrial BER that provides an optimal substrate for subsequent ga

107 weak against the 5'-AMP-dRP block in a model BER substrate, and this activity was not able to complem

108 th OGG1, and that SIRT1 indirectly modulates BER of 8-oxoG by controlling RECQL4-OGG1 interaction.

109 These studies also suggest that most BER-generated DSBs will occur in linker DNA and in genom

110 NA lesions, suggesting that the relative NER/BER product ratios may depend on competitive BER and NER

111 t a role for the redistribution of nucleolar BER factors in determining cisplatin toxicity.

112 ice between long-patch and single-nucleotide BER, thereby modulating cellular sensitivity to DNA dama

113 mammalian cells induces the accumulation of BER intermediate substrates, chromosomal aberrations, an

114 Here, we performed a proteomic analysis of BER deficient human cells using stable isotope labelling

115 ic/apyrimidinic (AP) site damage, binding of BER proteins, and G4 structures revealed that oxidized b

116 y unrecognized mechanism for coordination of BER by p53, and its dysfunction in p53-inactivated cells

117 Step-by-step coordination of BER is facilitated by multiple interactions between enzy

118 c abnormalities resulting from deficiency of BER factors are due to DNA damage or impaired DNA demeth

119 ver, little is known about the enzymology of BER of altered in-tandem CpG dinucleotides; e.g. Tp8-oxo

120 Here, we report that the handoff of BER intermediates that occurs during the repair of naked

121 ctionally, knockdown of Tet or inhibition of BER in hippocampal neurons elevated excitatory glutamate

122 tone H3 acetylation during the initiation of BER on chromatin.

123 Model DNA intermediates of BER are shown to induce significant rearrangement of the

124 Levels of BER-initiating DNA glycosylases can vary between individ

125 This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer

126 nd purine base damage is by a sub-pathway of BER that requires both XRCC1 and PARP1.

127 endent and PARP1-independent sub-pathways of BER.

128 nucleosomes on the frequency and pattern of BER-dependent DSB formation, we incubated nucleosomes co

129 rdinating BER are well known, the process of BER in chromatin where DNA is compacted with histones, r

130 e of ALC1 or APEX1, incomplete processing of BER intermediates results in post-replicative DNA gaps a

131 methods to effectively quantify the rate of BER as a whole.

132 A prominent example is the central role of BER in mediating active DNA demethylation, a multistep p

133 Here we report that the DNA ligation step of BER is compromised after pol beta insertion of oxidized

134 histone acetylation on the initial steps of BER, we assembled nucleosome arrays consisting of homoge

135 nct roles in regulating the initial steps of BER.

136 However, population studies of BER capacity have been limited because most methods used

137 peroxynitrite, is an excellent substrate of BER only.

138 e NTHL1 gene predisposes to a new subtype of BER-associated adenomatous polyposis and CRC.

139 nucleosomes contribute to the suppression of BER-generated DSBs.

140 posed that the mechanistic link between OGG1-BER and proinflammatory gene expression is OGG1's guanin

141 a the DNA base excision repair pathway (OGG1-BER).

142 at the protein level, and also the impact on BER in vitro and in vivo.

143 owever, the effect of chromatin structure on BER protein recruitment to DNA damage sites in living ce

144 g it critical that they be 'handed' from one BER enzyme to the next in a coordinated fashion.

145 e major enzymes and mechanisms co-ordinating BER are well known, the process of BER in chromatin wher

146 eraction of NEIL1 with replication and other BER proteins is required for efficient repair of the rep

147 e syndrome group B protein, TFIIH, and other BER proteins.

148 ts, we propose a revised model of long-patch BER and a new key regulation point for pathway choice in

149 major sub-pathway of conventional long-patch BER that involves formation of a 9-nucleotide gap 5' to

150 ic switch, shunting repair toward long-patch BER upon correct dCMP incorporation, thus enhancing repa

151 s the fourth and final step in (short-patch) BER.

152 fy a PPI inhibitor, 26 PPIs in DDR pathways (BER, MMR, NER, NHEJ, HR, TLS, and ICL repair) are specif

153 involves impairment of the APE1 and POLbeta BER activities, partly effectuated by associated reducti

154 d HECTD1 as an important factor in promoting BER in chromatin.

155 l lyase, APE1, at abasic sites in a purified BER system, rendering them poor substrates for polymeras

156 on (16-QAM OFDM) data with a bit error rate (BER) of 3.1 x 10(-3) over a 60-cm free-space link.

157 rates on advancements to the bit error rate (BER) performance.

158 rmodal crosstalk, and system bit error rate (BER).

159 a-rates of more than 35 Gb/s (Bit Error Rate(BER) < 3.8 x 10(-3)) with a coverage area of 39 m(2) at

160 We provide evidence for reduced BER efficiency in lamin A/C-depleted cells (Lmna null ME

161 expression by small interfering RNA reduces BER efficiency and leads to higher sensitivity to MMS an

162 with PARG inhibition synergistically reduces BER capacity in independently derived LNCaP and LAPC4 pr

163 e 38 was previously hypothesized to regulate BER during CSR, as the AID phosphorylation mutant, AID(S

164 Thus, we demonstrate that RAD9 regulates BER by controlling NEIL1 protein levels, albeit by diffe

165 , a core enzyme in base excision DNA repair (BER) of DNA lesions, specifically interacts with NPM1 wi

166 lved in base and nucleotide excision repair (BER and NER).

167 and H3 N-tails rescues base excision repair (BER) activity but not MMS sensitivity.

168 kylating agent-induced base excision repair (BER) and formation of DPCs is enhanced by a PARP inhibit

169 ase (AID) and requires base excision repair (BER) and mismatch repair (MMR).

170 lementary roles of the base excision repair (BER) and mismatch repair pathways, respectively, in CSR.

171 and the efficiency of base excision repair (BER) and RER enzymes (OGG1, MUTYH, and RNase H2) when pr

172 trand breaks (DSBs) by base excision repair (BER) and then quickly repaired by ligase (Lig)3-mediated

173 air pathways including base excision repair (BER) are also employed by mammalian cells for targeted e

174 fficient processing by base excision repair (BER) are among the factors suggested to contribute to TN

175 ng strands, initiating base excision repair (BER) by 8-oxoguanine DNA glycosylase (OGG1), yielding an

176 a) plays a key role in base excision repair (BER) by filling in small gaps that are generated after b

177 ylase, which initiates base excision repair (BER) by removing damaged DNA bases.

178 it has been shown that base excision repair (BER) can result in CAG repeat deletion from R-loops in y

179 activity and increases base excision repair (BER) efficiency.

180 Base Excision Repair (BER) efficiently corrects the most common types of DNA d

181 ther, depletion of the base excision repair (BER) enzyme DNA glycosylase augments PD-L1 upregulation

182 is shown that the DNA base excision repair (BER) enzyme, DNA glycosylase NEIL1, efficiently recogniz

183 ing DNA strands by the base excision repair (BER) enzymes can produce double-strand DNA breaks (DSBs)

184 chondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (Polg

185 ognition of 5'-AODN by base excision repair (BER) enzymes.

186 Base excision repair (BER) functions not only in the maintenance of genomic in

187 nsense mutation in the base-excision repair (BER) gene NTHL1.

188 air, but a role in DNA base excision repair (BER) has not been described.

189 ylation contributes to base excision repair (BER) in cells, their exact mechanistic role remains uncl

190 d to be substrates for base excision repair (BER) in the framework of active demethylation.

191 agments in addition to base excision repair (BER) incision products.

192 Base excision repair (BER) initiated by alkyladenine DNA glycosylase (AAG) is

193 damage is repaired by base excision repair (BER) initiated by alkyladenine DNA glycosylase (AAG).

194 APTX activity, blocked base excision repair (BER) intermediates containing the 5'-AMP or 5'-adenylate

195 Base excision repair (BER) is an essential DNA repair pathway involved in the

196 genes associated with base excision repair (BER) is increased with prostate cancer progression and c

197 Base excision repair (BER) is one of several DNA repair pathways found in all

198 Base excision repair (BER) is one of the most frequently used cellular DNA rep

199 Furthermore, base excision repair (BER) is responsible for causing CAG repeat contractions

200 Base excision repair (BER) is the major cellular DNA repair pathway that recog

201 Base excision repair (BER) is the major cellular pathway responsible for repai

202 OGG1 initiated base excision repair (BER) is the major pathway for repair of oxidative DNA ba

203 Base excision repair (BER) is the predominant pathway for coping with most for

204 lase1 (OGG1)-initiated base excision repair (BER) is the primary pathway to remove the pre-mutagenic

205 ortive ligation during base excision repair (BER) leads to blocked repair intermediates containing a

206 Base excision repair (BER) maintains genomic stability through the repair of D

207 ese maps revealed that base excision repair (BER) of alkylation damage is significantly modulated by

208 Base excision repair (BER) of an oxidized base within a trinucleotide repeat (

209 nitiate prereplicative base excision repair (BER) of oxidized bases in the replicating genome, thus p

210 uent activation of the base excision repair (BER) pathway drive the spatiotemporal formation of G4 st

211 The base excision repair (BER) pathway historically has been associated with maint

212 damaged bases via the base excision repair (BER) pathway is a long-standing question.

213 The base excision repair (BER) pathway is an important DNA repair pathway and is e

214 The base excision repair (BER) pathway is mainly responsible for repairing oxidize

215 ally, we find that the base excision repair (BER) pathway is required to maintain expression of AREG

216 The DNA base excision repair (BER) pathway is the frontline mechanism handling the maj

217 r of these lesions via base excision repair (BER) pathway maintains genomic fidelity.

218 ced DNA lesions by the base excision repair (BER) pathway prevents mutation, a form of genomic instab

219 The base excision repair (BER) pathway repairs oxidized lesions in the DNA that re

220 cancer cells, but the base excision repair (BER) pathway they trigger can also produce toxic interme

221 key enzyme in the DNA base excision repair (BER) pathway, is pivotal in maintaining the integrity an

222 osylase1 (OGG1) during base excision repair (BER) pathway.

223 functions through the base excision repair (BER) pathway.

224 he initial step in the base excision repair (BER) pathway.

225 lesions as part of the base excision repair (BER) pathway.

226 ethylation through the base-excision repair (BER) pathway.

227 the first step of the base excision repair (BER) pathway.

228 ision repair (NER) and base excision repair (BER) pathways work in a cooperative manner in the remova

229 Base excision repair (BER) processes non-helix distorting lesions (e.g., uraci

230 e to inhibitors of the base excision repair (BER) protein poly (ADP-ribose) polymerase (PARP).

231 known as a key nuclear base excision repair (BER) protein, in mitochondrial protein extracts derived

232 Base excision repair (BER) recognizes and repairs minimally helix-distorting D

233 unknown if subsequent base excision repair (BER) steps function on replication-associated ssDNA.

234 eta is a key enzyme in base excision repair (BER), an important repair system for maintaining genomic

235 idized bases in DNA is base excision repair (BER), and in vertebrates DNA polymerase beta (pol beta)

236 tral player in the DNA base excision repair (BER), and this physical complex not only promotes the po

237 onuclease in mammalian base excision repair (BER), apurinic/apyrimidinic endonuclease 1 (APE1).

238 primarily processed by base excision repair (BER), either initiated by uracil-DNA glycosylase (UNG) o

239 ibute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair

240 ir intermediate during base excision repair (BER).

241 lesions are subject to base excision repair (BER).

242 luenced by IFN-induced base excision repair (BER).

243 ays a critical role in base excision repair (BER).

244 ld also be involved in base excision repair (BER).

245 endent MUTYH-initiated base excision repair (BER).

246 s vitally important in base excision repair (BER).

247 y perturbing canonical base excision repair (BER).

248 otide insertion during base excision repair (BER).

249 (8-oxoG), repaired by base excision repair (BER).

250 in DNA are subject to base excision repair (BER).

251 onsible for initiating base excision repair (BER).

252 a noncanonical role in base excision repair (BER).

253 d in promoters via the base excision repair (BER)/single-strand break repair (SSBR) pathway.

254 These results reveal BER enzyme specificities enabling suppression of OGG1-in

255 lating the nucleolar localization of several BER enzymes.

256 Whether single nucleotide (SN)-BER of a damaged base requires histone deposition or nuc

257 sion to 1 nt, suggesting a preference for SP BER.

258 We investigated whether UV-DDB can stimulate BER for these two common forms of DNA damage, 8-oxoG and

259 main are similar in their ability to support BER in vitro The dRP lyase activity in both of these pro

260 n cell culture (SILAC), and demonstrate that BER deficiency, which induces genetic instability, resul

261 These results suggest the possibility that BER mediated toxic strand breaks are produced in cells u

262 We have previously shown that BER in a TNR hairpin loop can lead to removal of the hai

263 The BER enzyme methyl-CpG binding domain protein 4 (MBD4) ha

264 The BER pathway is widely used to repair DNA damage in cells

265 mice provide evidence that MSH2-MSH3 and the BER machinery promote trinucleotide repeat (TNR) expansi

266 Ku70 coordinate 2-way crosstalk between the BER and NHEJ pathways.

267 In R137Q knock-in mouse embryos, the BER efficiency was severely impaired, which subsequently

268 remove the 5'-adenylated-dRP group from the BER intermediate.

269 However, the mechanism(s) governing the BER process are poorly understood.

270 tion of oxidized purine nucleotides into the BER intermediate in vitro.

271 PRs in mice lacking the BER-initiating DNA glycosylase AAG did not exhibit alkyl

272 e at the final ligation step to maintain the BER efficiency.

273 c of many cancers, leads to a failure of the BER coordination mechanism, overexpression of APE1, accu

274 hich MSH2-MSH3 is used as a component of the BER machinery to cause expansion.

275 we discuss the newly identified roles of the BER pathway and examine the structural and mechanistic f

276 APE1 acetylation is an integral part of the BER pathway for maintaining genomic integrity.

277 Regulation of the BER pathway for mutagenic oxidized bases, initiated by N

278 osylases that catalyze the first step of the BER pathway, i.e. recognition and excision of DNA lesion

279 e of APE1 as a representative protein of the BER pathway, our data suggest a function for BER protein

280 Situated within the middle of the BER pathway, Pol beta must efficiently locate its substr

281 nderstanding the fundamental features of the BER pathway.

282 nderlying coordination and regulation of the BER process.

283 L1 is negatively correlated with that of the BER/single-strand break repair (SSBR) and tumours with l

284 s therefore play key roles in regulating the BER pathway and are consequently crucial for coordinatin

285 Our results demonstrate that the BER DNA ligases are compromised by subtle changes in all

286 Our results suggest that the BER enzyme, APE1, has acquired distinct surface residues

287 d oxidative base damage by irradiation, then BER-mediated DSBs become essential in triggering the che

288 protecting against contractions, but through BER rather than nucleotide excision repair.

289 is and the resolution of TNR R-loops through BER.

290 e containing-nucleosomes, allowing access to BER enzymes.

291 s, the NTHL1-associated lyase contributes to BER, even in the presence of APE1.

292 ling BER protein levels, 2) regulating total BER capacity, and 3) modulating the nucleolar localizati

293 cells, suggesting that genetically unstable BER deficient cells may be a source of pre-cancerous cel

294 -Crick-like dGTP insertion opposite T, using BER DNA ligases in vitro.

295 rate that TNR expansion can be prevented via BER in hairpin loops that is coupled with the removal of

296 ning DNA appears to be a suicidal event when BER is overwhelmed or disrupted.

297 While BER is well studied on naked DNA, it remains unclear how

298 el role for NPM1 as a modulator of the whole BER pathway by 1) controlling BER protein levels, 2) reg

299 onstitutive association of demethylases with BER/SSBR proteins in multiprotein complexes underscores

300 Within BER, AP-endonuclease 1 (APE1) is a multifunctional enzym