ライフサイエンスコーパス: mutator

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

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

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

4 ability in populations containing or lacking mutators.

5 playing roles as target-directed, purposeful mutators.

6 ffect i is typically small for strong-effect mutators.

7 ily have been identified as potent viral DNA mutators.

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

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

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

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

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

13 The mutator activity of the dgt mutants displays an unusual

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

15 No deficiency was noted in spontaneous mutator activity, allelic recombination or meiosis.

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

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

18 Since mutator adenoviruses can accumulate compound mutations t

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

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

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

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

23 llularity discourages selection against weak mutator alleles for reasons associated with both the cel

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

25 In principle, the fixation of mutator alleles is limited by (i) competition with mutat

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

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

28 Mutator alleles, which elevate an individual's mutation

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

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

31 lon and delta proofreading suppress discrete mutator and cancer phenotypes.

32 One mutator and one nonmutator series were sequenced at mism

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

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

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

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

37 sed carbon and reactive oxygen management in Mutator anthers.

38 Mutators are continually produced from nonmutators, ofte

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

40 xation probability Pfix of an initially rare mutator as a function of population size N, beneficial a

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

42 sessed directly by using an Escherichia coli mutator assay.

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

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

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

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

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

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

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

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

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

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

53 ed DNA damage, resulting in the survival of "mutator" cells.

54 Mutator class genes are required for siRNA-mediated RNA

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

56 -1 largely overlap with the targets of other mutator class genes; however, the mut-14 smut-1 double m

57 The mutator complex localizes to Mutator foci adjacent to P

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

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

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

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

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

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

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

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

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

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

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

72 describe the mechanism of this extraordinary mutator effect.

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

74 lication and, hence, account for the overall mutator effects.

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

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

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

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

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

80 vation-induced cytidine deaminase (AID) is a mutator enzyme that initiates somatic mutation and class

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

82 Mutators exhibited loss of severalfold more genes having

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

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

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

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

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

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

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

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

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

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

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

94 increased rate of alterations caused by each mutator gene.

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

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

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

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

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

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

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

102 These mutators gradually accumulate deleterious mutations, lim

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

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

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

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

107 Several mutators in this collection were found to have an insert

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

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

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

111 A mutator is an allele that increases the mutation rate th

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

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

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

115 Mutator-like transposable elements (MULEs) are widesprea

116 Mutator-like transposable elements (MULEs) are widesprea

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

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

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

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

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

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

123 present transcription factors derived from a Mutator-like transposase(s).

124 FHY3, FAR1, and Mutator-like transposases also share a similar domain st

125 ins sharing significant sequence homology to Mutator-like transposases, act as novel transcription fa

126 Active Mutator lines appear to experience chronic stress, on a

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

128 ors such as natural selection, linkage, or a mutator locus are affecting a given sequence.

129 A novel mutator locus in Escherichia coli was identified from a

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

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

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

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

137 e premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-direct

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

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

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

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

142 levels of point mutations of mtDNA, the POLG mutator mouse harbours linear mtDNAs.

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

144 to progeroid phenotypes came from the mtDNA mutator mouse.

145 t explain the progeroid features of the POLG mutator mouse.

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

147 gh-copy transposable element systems such as Mutator (Mu) in maize (Zea mays) afford the advantage of

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

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

150 e of pericarp color1 (p1) was examined using Mutator (Mu) transposon-mediated mutagenesis.

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

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

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

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

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

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

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

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

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

160 ype drives carcinogenesis, drugs that target mutator pathways might prevent cancer by delay.

161 ed into the 5' end of mutL correlates with a mutator phenotype (10(-7) to 10(-8) mutation/generation,

162 Instead, cancer cells express a mutator phenotype (i.e., the mutation rate in the cancer

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

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

165 riophage is a novel method for achieving the mutator phenotype and may allow the organism to respond

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

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

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

169 TP pool imbalance is not responsible for the mutator phenotype associated with the loss of ndk functi

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

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

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

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

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

175 fically with MutS and MutL and show that the mutator phenotype conferred by amino acid substitution w

176 Lastly, (e) if a mutator phenotype drives carcinogenesis, drugs that targ

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

178 rn genetic stability could be the cause of a mutator phenotype exhibited by human cancers.

179 f polymerase mutants that show an asymmetric mutator phenotype for certain mispairs, allowing an unam

180 A mutator phenotype has been proposed to account for this

181 The mutator phenotype hypothesis was postulated more than 40

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

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

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

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

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

187 The mlh3-D523N mutant also displayed a mutator phenotype in vegetative growth that was similar

188 (b) A mutator phenotype increases the efficiency of acquiring

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

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

191 e in dNTP pool levels is responsible for the mutator phenotype of an E. coli ndk mutant.

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

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

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

195 ing a biochemical rationale for the observed mutator phenotype of rev3-L979F yeast strains.

196 The mutator phenotype of the low-fidelity derivatives correl

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

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

199 lerance and activation initiates a transient mutator phenotype that may provide opportunities for ada

200 ts and predominantly G:C-->A:T and A:T-->G:C mutator phenotype typical for MNNG-induced unrepaired le

201 A mutator phenotype was observed in the hPMS2-deficient ce

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

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

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

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

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

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

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

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

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

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

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

215 This might partly explain the mitochondrial mutator phenotype.

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

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

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

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

220 correlates with their ability to induce the mutator phenotype.

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

222 tion of Pol II and Pol IV restored the Pol V mutator phenotype.

223 genic and commensal bacteria, resulting in a mutator phenotype.

224 with 5-bp gapped DNA, H285D showed a slight mutator phenotype.

225 MMR activity to inhibit apoptosis and induce mutator phenotype.

226 that disrupt these interactions result in a mutator phenotype.

227 he downstream gene (mutL) and resulting in a mutator phenotype.

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

229 The mutant also displayed a mutator phenotype.

230 high intracellular dNTP levels restored the mutator phenotype.

231 ing that EBV infection induced an epigenetic mutator phenotype.

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

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

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

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

236 Mutator phenotypes create genetic diversity that fuels t

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

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

239 g c-Abl kinase because increased survival of mutator phenotypes may be an unwanted consequence.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 bacteria with mutagens, for the evolution of mutator strains in bacterial populations, and also for t

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

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

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 Mutators that increase the mutation rate by the order of

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

299 duced cytidine deaminase (AID), a potent DNA mutator whose expression and function are highly regulat

300 les us to predict the conditions under which mutators will be evolutionarily favored.

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