ライフサイエンスコーパス: mutator

1 tion-induced cytidine deaminase (AID), a DNA mutator.

2 A mutator but does not equally create an RNA mutator.

3 cells and is considered to be a general gene mutator.

4 ily have been identified as potent viral DNA mutators.

5 ability in populations containing or lacking mutators.

6 playing roles as target-directed, purposeful mutators.

7 tes, leads to rapid induction of the genomic mutator activation-induced cytidine deaminase (AID) and

8 The antibody gene mutator activation-induced cytidine deaminase (AID) prom

9 ption complex-dependent targeting of the DNA mutator activation-induced cytidine deaminase (AID).

10 Recent studies have revealed that AID's DNA mutator activity is regulated by the RNA exosome complex

11 that have been attributed to the endogenous mutator activity of APOBEC3B (A3B), a member of the AID/

12 AID is highly expressed, and has an inherent mutator activity that helps generate antibody diversity.

13 k of correlation between AID binding and its mutator activity, providing evidence for the presence of

14 activation-induced cytidine deaminase (AID) mutator activity.

15 Since mutator adenoviruses can accumulate compound mutations t

16 ing RNA polII pausing with regulation of the mutator AID protein.

17 tation spectra produced by the pol3-01,L612M mutator allele, suggesting that they alter nucleotide se

18 merous evolution experiments have shown that mutator alleles (modifiers that elevate the genomic muta

19 ics of the balance between the production of mutator alleles and their elimination due to deleterious

20 alyze the circumstances in which fixation of mutator alleles is likely.

21 ther, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Poldelta, an

22 st range expansion, including recombination, mutator alleles, and mutational robustness.

23 Mutator alleles, which elevate an individual's mutation

24 utation rate and support the conclusion that mutator and antimutator phenotypes correlate with reduce

25 ferences in replication fidelity, as well as mutator and antimutator strains, suggest that virus muta

26 One mutator and one nonmutator series were sequenced at mism

27 These results define PGBD5 as an oncogenic mutator and provide a plausible mechanism for site-speci

28 arge series of pairwise competitions between mutator and wild-type strains under conditions where, in

29 ins have been identified as potent viral DNA mutators and have broad antiviral activity.

30 ance in comparison to mismatch-repair (mutS) mutators, and leads to new resistance genotypes.

31 e or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions.

32 Mutators are continually produced from nonmutators, ofte

33 , giving context to additional study of this mutator as a cancer biomarker or putative drug target.

34 e used papillation as a tool for finding new mutators as the mutators generate elevated levels of pap

35 sessed directly by using an Escherichia coli mutator assay.

36 -editing endonucleases as well as endogenous mutators at nucleotide resolution.

37 sible for the observed mutations in the mutT mutator background and those that occur after treatment

38 tation frequencies are not reduced in a mutY mutator background or after treatment with 2-aminopurine

39 ymerase active-site mutants as a "sensitized mutator background." Among the genes identified in our s

40 an outbreak caused by a naturally occurring mutator bacterial pathogen provides a dramatic example o

41 ot known to which protein networks these DNA mutators belong.

42 lude that the absence of MutT produces a DNA mutator but does not equally create an RNA mutator.

43 Mutators can invade a population by hitchhiking with a s

44 mutators, so they cannot stably invade, the mutators can still occasionally generate beneficial muta

45 tational idiosyncrasy displayed by different mutators, can play a major role in this process.

46 such as TP53, PRKDC, BRCA1/2 as well as new mutator candidates PPP2R2A and the chromosomal region 22

47 oth were wild type with respect to mutL, but mutators carried an 8-bp mutS deletion causing a framesh

48 Only haploid mutator cells with significant lifetime mutation accumul

49 Mutator class genes are required for siRNA-mediated RNA

50 expressed in the germline and, unlike other mutator class genes, are specifically required for RNAi

51 -1 largely overlap with the targets of other mutator class genes; however, the mut-14 smut-1 double m

52 piRNA pathway and siRNA amplification by the mutator complex are unknown.

53 The mutator complex localizes to Mutator foci adjacent to P

54 genes are targeted for RNA silencing by the mutator complex, a specialized small interfering RNA (si

55 ion of piRNA target genes is mediated by the mutator complex, which synthesizes high levels of siRNAs

56 ites of piRNA-dependent mRNA recognition and mutator complex-dependent siRNA amplification, respectiv

57 wnstream of piRNA production and upstream of mutator complex-dependent siRNA biogenesis.

58 pathway and promoting mRNA regulation by the mutator complex.

59 f MUT-14 is RNAi defective in vivo; however, mutator complexes containing the mutant protein retain t

60 implicated APOBEC3B as the more likely major mutator deaminase, whereas the role of APOBEC3A is not e

61 This comprehensive analytical approach of mutator defects provides a model to understand how genom

62 er the strength nor the sign of selection on mutators depend on their initial frequency, and while th

63 Cytidine deaminases are single stranded DNA mutators diversifying antibodies and restricting viral i

64 from the action of specialized trans-lesion mutator DNA polymerases; cells can join broken chromosom

65 induced-cytidine deaminase (AID) and the A-T mutator, DNA polymerase eta, respectively, in mutagenesi

66 to produce such a driver mutation before non-mutators do.

67 transposition is mediated by the autonomous Mutator-Don Robertson (MuDR) element.

68 The recent discovery of a mutator effect associated with deletion of dgt indicated

69 osity for the variant allele caused a strong mutator effect comparable with that of complete MMR defi

70 t strain, a topoisomerase I (Top1)-dependent mutator effect develops with accumulation of short delet

71 ions in dNTP metabolism genes eliminated the mutator effect of pol3-R696W, whereas restoration of hig

72 bined with a MMR defect, indicating that the mutator effect of POLD1-R689W results from a high rate o

73 The suppression of the recA730 mutator effect was alleviated in a lexA-deficient backgr

74 he Escherichia coli dnaX36 mutant displays a mutator effect, reflecting a fidelity function of the dn

75 OS expression as well as a spontaneous (SOS) mutator effect.

76 describe the mechanism of this extraordinary mutator effect.

77 s of the most common variant, P286R, produce mutator effects far exceeding the effect of Pole exonucl

78 Severe mutator effects of the most common variant, Polepsilon-P

79 d repeats similar in length and structure to Mutator elements, some display subterminal inverted repe

80 ay increase following secondary infection or mutator emergence, we sought to ascertain the incidence

81 lly from repetitive activation of the B cell mutator enzyme AID.

82 ificant promiscuous targeting of this B-cell mutator enzyme genome-wide.

83 vation-induced cytidine deaminase (AID) is a mutator enzyme that initiates class switch recombination

84 vation-induced cytidine deaminase (AID) is a mutator enzyme that targets immunoglobulin (Ig) genes to

85 Mutators exhibited loss of severalfold more genes having

86 d the maize brittle stalk4 (bk4) mutant in a Mutator F2 population.

87 The mutator complex localizes to Mutator foci adjacent to P granules at the nuclear perip

88 The Mutator foci are adjacent to P granules but are not depe

89 ranules at the nuclear pores and perinuclear Mutator foci contribute to target mRNA surveillance and

90 ng the mutator proteins, and in its absence, Mutator foci fail to form at the nuclear periphery.

91 UT-16 at Mutator foci, suggesting a role for Mutator foci in siRNA amplification.

92 initiating siRNA amplification in germ cell Mutator foci, possibly through the recruitment or retent

93 The RdRP RRF-1 colocalizes with MUT-16 at Mutator foci, suggesting a role for Mutator foci in siRN

94 subcellular foci adjacent to P granules and Mutator foci, two phase-separated condensates that are t

95 enriched in RSD-6 but are excluded from the Mutator foci.

96 lineage yet functions separately as a potent mutator for genomic DNA.

97 suggest that the down-regulation of the MMR mutator gene associated with miR-21 overexpression may b

98 Evidence is presented regarding the role of mutator gene mutL(-) in the establishment of diversity a

99 increased rate of alterations caused by each mutator gene.

100 on as a tool for finding new mutators as the mutators generate elevated levels of papillation.

101 We found that most mutator genes alter early during tumorigenesis and were

102 s the first computational method to identify mutator genes and to take into account the increase of t

103 This method also identifies mutator genes which increase genomic instability when th

104 count the increase of the alteration rate by mutator genes, providing more accurate estimates of the

105 of persisters are analogous to the so-called mutator genes; they modulate the rate at which these err

106 uch weaker than that of mutational biases in mutator genomes.

107 mmunities, including the rapid appearance of mutator genotypes.

108 These mutators gradually accumulate deleterious mutations, lim

109 , and pre-steady-state kinetics to compare a mutator (H273R) RdRp from poliovirus to the wild-type (W

110 rmore, its potential to act as a genomic DNA mutator has implications for a role in carcinogenesis.

111 This raises the interesting question of how mutator hitchhiking is suppressed or its phenotypic effe

112 ncy further complicates our understanding of mutators in clinical settings, as well as their role in

113 ive effects of mutations caused by different mutators in species with different GC compositions.

114 ill often be many "young," recently produced mutators in the population, and the fact that deleteriou

115 ) PPR gene, MPPR6, which was isolated from a Mutator-induced collection of maize kernel mutants by a

116 insertions within exons and introns, whereas Mutator insertions are more enriched in promoters and 5'

117 Comparison of Ds and Mutator insertions reveals distinct target preferences,

118 suggesting that the competitive advantage of mutators is due to a greater probability of developing s

119 Pack-MULEs, nonautonomous Mutator-like elements (MULEs) that carry genic sequence(

120 evious reports, we observe that the putative Mutator-like transposable element-derived genes are gene

121 Mutator-like transposable elements (MULEs) are widesprea

122 Mutator-like transposable elements (MULEs) are widesprea

123 Here we show that Pack-Mutator-like transposable elements (Pack-MULEs) that car

124 Furthermore, we determine that Mutator-like transposable elements capture parental sequ

125 the evolution of putative genes derived from Mutator-like transposable elements in ten Oryza species

126 demonstrate that putative genes derived from Mutator-like transposable elements tend to be expressed

127 Mutator-like transposable elements, a class of DNA trans

128 rvival, and regulation of genes derived from Mutator-like transposable elements, thus contributing to

129 and 20-fold coverage one wild-type and three mutator lines using Illumina Solexa 36-bp reads.

130 genomes, and suggests the APOBEC3 family of mutators may target the LGST in the human genome.

131 The mtDNA-mutator mice acquire somatic mtDNA mutations via a targe

132 e absence of Parkin, dopaminergic neurons in Mutator mice degenerated causing an L-DOPA reversible mo

133 between groups, homozygous mitochondrial DNA mutator mice displayed elevated numbers of hypertrophic

134 al biogenesis and function, in the muscle of mutator mice increased mitochondrial biogenesis and func

135 ncoordinated 51-like kinase (ULK) 1 in mtDNA-mutator mice resulted in proteasome-mediated degradation

136 These results suggest that mitochondrial mutator mice undergo a specific loss of mitochondrial co

137 prove some premature aging phenotypes in the mutator mice without reverting the accumulation of mtDNA

138 n accelerated generation of mtDNA mutations (Mutator mice).

139 ted ubiquitin was increased in the brains of Mutator mice, indicating PINK1-Parkin activation.

140 erythroid progenitors of wild-type and mtDNA-mutator mice.

141 nd development of macrocytic anemia in mtDNA-mutator mice.

142 erly or predict respiratory insufficiency in mutator mice.

143 roteome of heart and skeletal muscle of aged mutator mice.

144 ation in hematopoietic cells from aged mtDNA-mutator mice.

145 The majority of downregulated proteins in mutator mitochondria were subunits of respiratory comple

146 V subunits, were unchanged or upregulated in mutator mitochondria, suggesting a robustness to mtDNA m

147 Here we describe a new mtDNA mutator model based on a mitochondrially-targeted cytidi

148 notypes make mito-APOBEC1 an excellent mtDNA mutator model for ageing research.

149 This TdT-mutator model successfully predicts the relative inciden

150 The mitochondrial mutator mouse is a well-established model of premature a

151 The mtDNA mutator mouse, a mouse model with a proofreading-deficie

152 to progeroid phenotypes came from the mtDNA mutator mouse.

153 hat of the PolgA(mut/mut) mitochondrial DNA 'mutator' mouse.

154 Mutator (Mu) elements, one of the most diverse superfami

155 Here, we constructed a Mutator (Mu) insertional library in the B73 inbred backg

156 Transposons of the Mutator (Mu) superfamily have been shown to play a criti

157 upted gene to a known phenotype in high-copy Mutator (Mu) transposon lines in maize.

158 In this study, we found that two independent mutator (Mu)-interrupted zmrs lines, containing no raffi

159 sults, it has been repeatedly suggested that mutators must be sufficiently frequent to produce such a

160 In Caenorhabditis elegans, mutator (mut) class genes mediate siRNA-guided repressio

161 We then chose the mutator mutant I174S for further study and found that it

162 red dNTP pools and increased mutation rates (mutator mutants).

163 The evolutionary fate of mutator mutations - genetic variants that raise the geno

164 erovar Typhimurium LT2 (nonmutator) and LT7 (mutator, mutL) strains after decades of storage in seale

165 We then consider how this mutator-nonmutator balance can be disrupted by beneficia

166 mRNAs and short non-coding RNAs, and also as mutators of hyper-variable genes, viruses and selfish el

167 nd AID acts as a transcription-dependent DNA mutator on these genes to improve antibody affinity and

168 helicase smut-1 functions redundantly in the mutator pathway with its paralog mut-14 during RNAi.

169 by miR-155 in which miR-155 promotes both a mutator phenotype and a cellular environment particularl

170 trate that rnh203 mutations result in a weak mutator phenotype and cause growth defects and synergist

171 NEIL1, whose deficiency causes a mutator phenotype and is activated during the S phase, i

172 roteins, hMSH2, hMSH6, and hMLH1, inducing a mutator phenotype and MSI.

173 em for BER which when compromised, confers a mutator phenotype and sensitizes cells to the cytotoxic

174 The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virule

175 ed chromosomal instability and DNA damage, a mutator phenotype associated with tumorigenesis in vivo

176 anges in Pol epsilon that reduced the pol2-4 mutator phenotype between 3- and 23-fold.

177 Here we demonstrate that a mutator phenotype caused by a mismatch repair defect is

178 ansgenic but not PKR null mice demonstrate a mutator phenotype characterized by radiation-induced and

179 BCNS-BCCs appear to have reduced mutator phenotype compared with sporadic BCCs, which may

180 east Polepsilon produced an unusually strong mutator phenotype exceeding that of proofreading-deficie

181 A mutator phenotype has been proposed to account for this

182 The mutator phenotype hypothesis was postulated more than 40

183 We find that the T362I RdRp exhibits a mutator phenotype in biochemical experiments in vitro.

184 h properties in cell culture but expresses a mutator phenotype in cells.

185 Disruption of this interaction causes a mild mutator phenotype in Escherichia coli, but completely ab

186 s such as hepatitis B virus, but can cause a mutator phenotype in many cancers.

187 Here we show that generation of a mutator phenotype in S. pneumoniae through deletions of

188 d also Ig class switching, can have a potent mutator phenotype in the development of lymphoma.

189 In contrast, the elg1Delta mutator phenotype is exacerbated by PCNA mutants that ac

190 The pol2-M644G mutator phenotype is partially suppressed by mrc1Delta b

191 tic data for the E288K variant show that its mutator phenotype is specific for misincorporating oppos

192 The remaining, still strong, mutator phenotype is synergistically elevated in an msh6

193 PCNA generally increases mutation rate, the mutator phenotype of elg1Delta is attenuated by PCNA mut

194 Deletion of DUN1 (dun1Delta) suppresses the mutator phenotype of pol2-4 (encoding Pol epsilon proofr

195 l2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Delta cells.

196 ent that could account for the unprecedented mutator phenotype of pol3-R696W strains.

197 The mutator phenotype of the low-fidelity derivatives correl

198 g that it included more viruses possessing a mutator phenotype rather than viruses possessing an anti

199 Human cancers driven by a mutator phenotype represent an intriguing model to test

200 ions per tumour, excluding four cases with a mutator phenotype that harboured inactivating mutations

201 (SARS)-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in

202 d, but not BRCA1-mutated cases, exhibited a "mutator phenotype" by containing significantly more muta

203 imilar to the mutations that can typify the 'mutator phenotype' of numerous tumors.

204 ions can dominate the mutational landscape ('mutator phenotype') of some cancers, however, the basis

205 -fold increase in spontaneous mutation rate (mutator phenotype), and inactivation of both Pol delta p

206 Elevated mutation rates (mutator phenotype), including simple repeat instability

207 to target DNA-repair proteins, leading to a mutator phenotype, and we find that over 93% of tumors i

208 1 mutations display AEE deficiency, a strong mutator phenotype, enhanced cellular transformation, and

209 Deletion of dgt creates a mutator phenotype, indicating that the dGTPase has a fid

210 geting tumor suppressor genes and inducing a mutator phenotype, miR-155 may allow the selection of ge

211 se defective DNA repair is associated with a mutator phenotype, the risk of transmission to the offsp

212 Some argue that cancers have a mutator phenotype, whereas others argue that the normal

213 lymerase epsilon (POLE-exo*) exhibit a novel mutator phenotype, with markedly elevated TCT-->TAT and

214 ing that EBV infection induced an epigenetic mutator phenotype.

215 us (PV) RdRp derivative (H273R) possessing a mutator phenotype.

216 the N-terminal domain is responsible for the mutator phenotype.

217 This might partly explain the mitochondrial mutator phenotype.

218 omas and found that colon adenomas exhibit a mutator phenotype.

219 r damaged bases, leading to the observed SNS mutator phenotype.

220 ption of yycJ or recJ leads to a spontaneous mutator phenotype.

221 correlates with their ability to induce the mutator phenotype.

222 the majority of the hAAG-Y127I/H136L-induced mutator phenotype.

223 i MutL and the beta-clamp only causes a mild mutator phenotype.

224 ucleotide selection to offset the pol3-L612M mutator phenotype.

225 elta; neither deletion suppresses the pol2-4 mutator phenotype.

226 The mutant also displayed a mutator phenotype.

227 high intracellular dNTP levels restored the mutator phenotype.

228 moral hypoxia has been proposed to create a "mutator" phenotype through downregulation of DNA repair,

229 its exonuclease activity, are connected with mutator phenotypes and cancer formation.

230 proofreading activity or MMR function cause mutator phenotypes and consequently increased cancer sus

231 spontaneous mutation frequencies; and, these mutator phenotypes correlated with the ability of the st

232 Mutator phenotypes create genetic diversity that fuels t

233 eatments targeting dNTP pools could modulate mutator phenotypes for therapy.

234 hat similar genetic interactions could drive mutator phenotypes in cancer cells.

235 e modeled the consequences of cancer-related mutator phenotypes on lifespan using yeast defective for

236 Strong diploid mutator phenotypes produced a form of genetic anticipati

237 for DNA topoisomerase I (topA) give rise to mutator phenotypes with characteristic mutational spectr

238 ression/copy number loss and may have severe mutator phenotypes with enhanced malignancies that are c

239 Our results suggest that, for S. mutans, mutator phenotypes, due to loss of BER enzymes, may conf

240 utation, which individually confer only weak mutator phenotypes, inactivates mismatch repair in the y

241 NTP pool deviations but exceptionally strong mutator phenotypes, when measured in a mutational forwar

242 s, we isolated nine polymerase variants with mutator phenotypes, which allowed us to probe the effect

243 le numbers of fixed mutations and a range of mutator phenotypes.

244 vidually suppress the pol3-01 and pol3-L612M mutator phenotypes.

245 of glycated DNA and RNA and exhibited strong mutator phenotypes.

246 PRR pathway, yielding hyper-recombinant and mutator phenotypes; analogous defects may underlie the g

247 in the young, preprogeroid polymerase gamma mutator (POLG) mouse produce a metabolic state of starva

248 aging phenotypes in prematurely aging mtDNA mutator (PolgA(mut/mut)) mice.

249 WT lyase activity and has been shown to be a mutator polymerase.

250 stitution at residue I174 that resulted in a mutator polymerase.

251 In strains encoding mutator polymerases, this reduction is preferential for

252 nt this limitation by analyzing genomes from mutator populations that arose during a long-term experi

253 o generate antibody diversity via the B-cell mutator protein activation-induced cytidine deaminase (A

254 We propose that the mutator proteins and RRF-1 constitute an RNA processing

255 Here we show that each of the six mutator proteins localizes to punctate foci at the perip

256 ormation of a protein complex containing the mutator proteins, and in its absence, Mutator foci fail

257 eaminase activity in an Escherichia coli DNA mutator reporter, whereas Y181A and Y182A mutants retain

258 Mutators represent a successful strategy in rapidly adap

259 Analysis of these mutators revealed not only strain-dependent increases in

260 of uncertain significance (VUS), focusing on mutator S homolog 2 (MSH2).

261 Site Directed Mutator (SDM) is a statistical potential energy function

262 To investigate the basis for mutator selection, we undertook a large series of pairwi

263 Mutator series were more likely to be multiply antibioti

264 dNTP pool levels correlate with Pol epsilon mutator severity, suggesting that treatments targeting d

265 ions where selection on average acts against mutators, so they cannot stably invade, the mutators can

266 encodes the mitochondrial NADH kinase, is a mutator, specific for mitochondrial genes.

267 ormation process is responsible for the "CNV-mutator state," and this state is dampened after early e

268 ere phenotyped for antibiotic resistance and mutator status and were genotyped by repetitive-sequence

269 Additionally, a mutator strain was identified.

270 chemical mutagens, ultraviolet light and the mutator strain XL1-Red under similar conditions.

271 Our results show that, although mutator strains are sufficiently fit when grown in large

272 in a WT and in nine Saccharomyces cerevisiae mutator strains deficient for distinct genome maintenanc

273 These mutator strains generate higher mutation frequencies tha

274 f two independently evolved Escherichia coli mutator strains that have accumulated deleterious mutati

275 These reductions in growth by mutator strains were ameliorated by growth at lower temp

276 ies have to date been reported in persistent mutator strains, which suffer from reduced genomic fidel

277 l, suggests the existence of M. tuberculosis mutator strains.

278 We identified well known mutators such as TP53, PRKDC, BRCA1/2 as well as new mut

279 rovide evidence for its inclusion within the Mutator superfamily.

280 at there are polymerase-specific pathways of mutator suppression.

281 ation spectra suggest multiple mechanisms of mutator suppression.

282 es of DNA mutation patterns resulting from a mutator that displays hot/cold-spots, substitution prefe

283 when deleterious mutation rates are high in mutators, there will often be many "young," recently pro

284 ROS sensitivity, highlights the potential of mutators to drive pathoadaptation in the host and serve

285 ia its own interactors and links the A3A DNA mutators to the Rb-BRCA1-ATM network.

286 cteristic of the DNA binding domain (DBD) of Mutator transposases and of several transcription factor

287 ylation in exons (8%) may deter insertion of Mutator transposon insertion, while CHG methylation at s

288 Maize lines lacking RAF1 due to Mutator transposon insertions are Rubisco deficient and

289 Three novel Mez1 alleles containing Mutator transposon insertions within the promoter were i

290 However, the identification of Mutator transposons in other eukaryotes has been quite l

291 alysis reveals two distinct tumor types: the mutator type is positively associated with potential res

292 experimental evolution, populations of both mutator types exhibited comparable improvements in fitne

293 eplication errors generated by an asymmetric mutator variant of DNA polymerase delta (Pol delta).

294 Here, using budding yeast, we show that mutator variants of Pol epsilon depend on damage uninduc

295 Using this mutator vector, we demonstrate rapid selection of resist

296 rate compares favourably with error-rates of mutator versions of animal gamma DNA polymerases.

297 Making error-prone mutator versions of gamma DNA polymerases revolutionised

298 Mutators were the most frequent winners but wild-type st

299 MR) and oxidized guanine (GO) system, termed mutators, which exhibit increased spontaneous-mutation f

300 The mutational specificity of the new mutator yycJ is similar to that of mismatch repair-defic