ライフサイエンスコーパス: AID

1 AID binds directly to switch RNA through G-quadruplexes

2 AID deamination is not exclusive to immunoglobulin loci;

3 AID expression is tightly regulated in B cells and its o

4 AID inhibition using lentiviral-encoded short hairpin (s

5 AID is essential for the maturation of antibodies and ca

6 AID mediates class-switch recombination (CSR) and somati

7 AID scans randomly when constrained in an 8 nt model bub

8 AID target genes are enriched in chromatin modifications

9 AID was expressed in human primary keratinocytes in an i

10 AID-Cre(+) GNA13-deficient mice demonstrate disordered G

11 AID/APOBEC family enzymes are best known for deaminating

12 We show that the sigma(54) AID becomes structured after associating with the core l

13 n initiation, we characterized the sigma(54) AID by NMR spectroscopy and other biophysical methods an

14 ium fluoride, we studied the NtrC1-sigma(54) AID complex using NMR spectroscopy.

15 construct of the Aquifex aeolicus sigma(54) AID that consists of two predicted helices and retains n

16 We found that deficient pS38 abated AID chromatin association and CSR but not mutation at My

17 that IGHV3-23*01 in Ramos cells accumulates AID-induced mutations primarily in the AGCT in CDR2, whi

18 In addition, through off-target activity, AID has a much broader effect on genomic instability by

19 frequencies of SHM in memory B cells from AD-AID patients and AID+/- subjects, who were unable to pre

20 ts with autosomal dominant AID mutations (AD-AID), asymptomatic AICDA heterozygotes (AID+/-), and pat

21 irectly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B

22 Using lithium and an AID-S38 phospho mutant, we compared the role of pS38 in

23 ility in normal and neoplastic B cells by an AID-dependent mechanism.

24 ptosis-control genes FAS/CD95, Caspase-2 and AID.

25 equences in regulating Ab gene diversity and AID targeting specificity.

26 oRNAs (miRs) contribute to decreased E47 and AID in aged B cells.

27 Our data indicate that E47 and AID mRNA stability is lower in stimulated B cells from e

28 of which displayed somatic hypermutation and AID-mRNA expression.

29 ssion and translocation frequency to IGH and AID off-target sites in human chronic lymphocytic leukae

30 M in memory B cells from AD-AID patients and AID+/- subjects, who were unable to prevent the accumula

31 The enzymes RAG1-RAG2 and AID, which diversify immunoglobulin-encoding genes, are

32 This V(D)J selection and AID-mediated diversification operate comparably in germ-

33 inducing both Igh germline transcription and AID expression.

34 end AIDS by 2030, with incidence of HIV and AIDs-related mortality rates both at less than one event

35 is to favor mature B cell lymphomas that are AID dependent and show chromosome translocations.

36 Furthermore, BALB/c aorta grafts from B6 AID(-/-) recipient mice on day 30 after transplantation

37 ALB/c mouse aortas were transplanted into B6 AID(-/-) mice with or without FK506 treatment.

38 Splenocytes from C57BL/6 J (B6) AID(-/-) mice were used for determining in vitro prolife

39 nmask a striking lack of correlation between AID binding and its mutator activity, providing evidence

40 Despite the functional link between AID and TET in epigenetic gene regulation, the role of A

41 tifs potentially function as spacers between AID deamination hotspots.

42 h DNA damage, suggesting that factors beyond AID association contribute to mutation targeting.

43 mutation hotspots are largely determined by AID deamination.

44 itch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted f

45 ion with frequent S-region DSBs initiated by AID.

46 The mutability modulated by AID hotspots and coldspots changes correlated only weakl

47 anism by which processing of G:U produced by AID at the telomeres can eliminate B cells at risk of ge

48 er noncoding regions potentially targeted by AID (combined 9411 nt), including the 5' untranslated re

49 onstrates the activities of canonical AID (c-AID), leading to clustered mutations near active transcr

50 me of onset, we find that while ageing and c-AID activities are ongoing, nc-AID-associated mutations

51 e transcriptional start sites; non-canonical AID (nc-AID), leading to genome-wide non-clustered mutat

52 res demonstrates the activities of canonical AID (c-AID), leading to clustered mutations near active

53 ed heightened humoral responses (CD20, CD22, AID) in melanoma.

54 Moreover, G4 substrates induce cooperative AID oligomerization.

55 onal interference, and gene deletion (CRISPR-AID) in the yeast Saccharomyces cerevisiae.

56 We demonstrate the application of CRISPR-AID not only to increase the production of beta-carotene

57 Guided by single guide (sg)RNAs, dCas9-AID-P182X (AIDx) directly changed cytidines or guanines

58 Aicda (which encodes the cytidine deaminase AID) and thus silenced B cell-specific gene expression,

59 nary precursors, the antibody gene deaminase AID and the RNA/DNA editing enzyme APOBEC1 (A1).

60 ve of activation-induced cytidine deaminase (AID) activity.

61 in an activation-induced cytidine deaminase (AID) and H2AX-dependent fashion.

62 ed by activation-induced cytidine deaminase (AID) and requires base excision repair (BER) and mismatc

63 that activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members r

64 Activation-induced cytidine deaminase (AID) converts cytosine into uracil to initiate somatic h

65 Activation-induced cytidine deaminase (AID) initiates both class switch recombination (CSR) and

66 Activation-induced cytidine deaminase (AID) initiates CSR by promoting deamination lesions with

67 Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglob

68 Activation-induced cytidine deaminase (AID) is a genome-mutating enzyme that initiates class sw

69 Activation-induced cytidine deaminase (AID) is a key regulator of class switch recombination an

70 Activation-induced cytidine deaminase (AID) is a mutator enzyme that targets immunoglobulin (Ig

71 Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two cen

72 human activation-induced cytidine deaminase (AID) to identify genes preventing R loops.

73 nt of activation-induced cytidine deaminase (AID) to Ig switch regions (S regions).

74 nt of activation-induced cytidine deaminase (AID) to S regions is critical for CSR; however, the unde

75 ng of activation-induced cytidine deaminase (AID) to the Igh locus.

76 9 to recruit variants of cytidine deaminase (AID) with MS2-modified sgRNAs, we can specifically mutag

77 on of activation-induced cytidine deaminase (AID) with nuclease-inactive clustered regularly interspa

78 press activation-induced cytidine deaminase (AID), a DNA mutator.

79 ls of activation-induced cytidine deaminase (AID), a key player in B-cell responses to antigen trigge

80 codes activation-induced cytidine deaminase (AID), display an impaired peripheral B cell tolerance.

81 ed by activation-induced cytidine deaminase (AID), the activity of which leads to DNA double-strand b

82 s are activation-induced cytidine deaminase (AID), the enzyme of class switch recombination and somat

83 Activation-induced cytidine deaminase (AID), the enzyme responsible for induction of sequence v

84 Activation-induced cytidine deaminase (AID), the enzyme-mediating class-switch recombination (C

85 on of activation-induced cytidine deaminase (AID)-instigated DNA double-strand breaks into the IgH lo

86 nzyme Activation-induced cytidine Deaminase (AID).

87 y the activation-induced cytidine deaminase (AID).

88 il by activation-induced cytidine deaminase (AID).

89 otein activation-induced cytidine deaminase (AID).

90 e DNA activation-induced cytidine deaminase (AID).

91 that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and sk

92 on of activation-induced cytosine deaminase (AID).

93 Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiati

94 Activation-induced deaminase (AID) can drive lymphomagenesis by generating off-target

95 Activation-induced deaminase (AID) converts DNA cytosines to uracils in immunoglobulin

96 roteins induce activation-induced deaminase (AID) expression in activated B cells.

97 Activation-induced deaminase (AID) functions by deaminating cytosines and causing U:G

98 Activation-induced deaminase (AID) initiates antibody gene diversification by creating

99 Activation-induced deaminase (AID) initiates mutagenic pathways to diversify the antib

100 doxically also activation-induced deaminase (AID) involved in somatic hypermutations/class switch rec

101 Activation-induced deaminase (AID) mediates the somatic hypermutation (SHM) of Ig vari

102 n is driven by activation-induced deaminase (AID), which converts cytidine to uracil within the Ig va

103 (SHM) enzyme, Activation Induced Deaminase (AID), which overlaps the CpG methylation site.

104 n targeting by activation-induced deaminase (AID).

105 es ["activity-regulated inhibitor of death" (AID) genes] including the transcription factor (TF) NPAS

106 hat MMSET-II inactivation leads to decreased AID recruitment and DSBs at the upstream donor Smu regio

107 ave adapted the auxin-inducible degradation (AID) system discovered in plants to enable conditional p

108 eered to contain the auxin-inducible degron (AID) are selectively degraded upon adding auxin.

109 most frequent splice variants (AID-DeltaE4a, AID-DeltaE) were detected in 128 (96.2%), 96 (72.2%), an

110 mately 20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable

111 equence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon.

112 ies in autoimmune and inflammatory diseases (AID) have uncovered hundreds of loci mediating risk.

113 Autoimmune diseases (AIDs) are polygenic diseases affecting 7-10% of the popu

114 We found that these earliest-diverged AID orthologs are active cytidine deaminases that exhibi

115 n unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over

116 gulatory domains, the autoinhibitory domain (AID) and calmodulin-binding domain (CBD), which block th

117 o discovered that an auto-inhibitory domain (AID) of Set2 primarily restricts Set2 activity to transc

118 inal sigma(54) activator interacting domain (AID).

119 t patients, patients with autosomal dominant AID mutations (AD-AID), asymptomatic AICDA heterozygotes

120 -GC B-cell lymphomas, the role of downstream AID-associated DNA repair pathways in the pathogenesis o

121 these before stimulation would decrease E47/AID upon cell activation.

122 ngle-stranded, thereby creating an effective AID substrate.

123 e switch (S) region is a much more efficient AID deamination target than the V region.

124 end-joining assay and apply it to endogenous AID-initiated S-region DSBs in mouse B cells.

125 Consistently, PI3Kdelta inhibitors enhanced AID expression and translocation frequency to IGH and AI

126 d cytoplasmic retention cooperate to exclude AID from the nucleus but might not be functionally equiv

127 We find that the existing AID / APOBEC hotspots have a large impact on retrotransp

128 cient B cells have reduced clonal expansion, AID expression, and capacities to yield IgG2c and high-a

129 he proliferation of tumor B cells expressing AID.

130 We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous ce

131 t the initial induction of IRF4 by RA favors AID expression.

132 First, we find AID targets SHM hotspots within V exon and S region pass

133 Odds ratio (OR) assessment for AID-directed therapies.

134 n; the transcription factor E47, crucial for AID expression; and the ability to generate optimal memo

135 at the transcriptional level of less E47 for AID.

136 ructures are not necessary intermediates for AID access.

137 tion factor 1 alpha (eEF1A) is necessary for AID cytoplasmic sequestering.

138 osis constitute an essential time window for AID-induced deamination, and provide a novel DNA damage

139 uced a synergistic effect in the grafts from AID(-/-) recipients with further reduction of intimal hy

140 direct targeting and induction of functional AID by EBNA3C, suggest a novel role for EBV in the etiol

141 at sequentially produce and store functional AID in the cytoplasm.

142 Furthermore, AID technology facilitated concurrent generation and phe

143 tures of maltose binding protein (MBP)-fused AID alone and in complex with deoxycytidine monophosphat

144 lobulin switch regions are particularly good AID substrates in vitro.

145 (AD-AID), asymptomatic AICDA heterozygotes (AID+/-), and patients with uracil N-glycosylase (UNG) de

146 a clinically used therapeutic, induced high AID pS38 levels.

147 Higher AID full-length transcript levels were significantly ass

148 to the lungs of patients suffering from HIV/AIDs.

149 How AID mediates central B cell tolerance remains unknown.

150 However, AID also deaminates nonimmunoglobulin genes, and failure

151 However, AID is mostly cytoplasmic, and how and exactly when it a

152 However, AID occupancy does not directly correlate with DNA damag

153 Here, we produced active human AID and revealed its preferred recognition and deaminati

154 ontrol of another mutagenic deaminase, human AID, and provides a rationale for its regulation.

155 escribed the biochemical properties of human AID and found that it is an unusual enzyme in that it ex

156 o damage from either the expression of human AID or increased oxidative stress.

157 Finally, using a hyperactive AID variant, we mutagenize loci both upstream and downst

158 and nonclonal mutations arise within non-Ig AID target genes in the combined absence of UNG and MSH2

159 ferred nucleic acid substrates, illuminating AID targeting mechanisms during CSR and SHM.

160 f these effects were completely abrogated in AID-deficient B cells.

161 b, showed increased somatic hypermutation in AID off-targets.

162 Here, we define a conformational motif in AID that dictates its cytoplasmic retention and demonstr

163 spho mutant, we compared the role of pS38 in AID activity at the Ig switch region and off-target Myc

164 Here, we analyzed B cell tolerance in AID-deficient patients, patients with autosomal dominant

165 his study indicate that inflammation-induced AID expression promotes skin cancer development independ

166 of Sox2 in splenic B cells severely inhibits AID expression and CSR, whereas deletion of Sox2 increas

167 passive transfer of antinucleosome IgG into AID(-/-)MRL/lpr mice elevated autoantibody levels and pr

168 Hence, B cell intrinsic AID expression mediates central B cell tolerance potenti

169 Igh locus AID-initiated lesions are processed by error-free and er

170 In activated B lymphocytes, AID initiates antibody variable (V) exon somatic hypermu

171 We discuss possible mechanisms AID and APOBEC viral targets have adopted to escape the

172 Median AID transcript levels were higher in lymph node material

173 ions induced as a consequence of misdirected AID in the partner oncogenes of IGH translocations, whic

174 Most AID is associated to unspecified cytoplasmic complexes.

175 However, most AID+ immature B cells lacked anti-apoptotic MCL-1 and we

176 riptional start sites; non-canonical AID (nc-AID), leading to genome-wide non-clustered mutations, an

177 ageing and c-AID activities are ongoing, nc-AID-associated mutations likely occur earlier in tumour

178 Interestingly, ectopically expressed nuclear AID in HeLa cells was preferentially found in the early

179 hypomorphic cells there was reduced nuclear AID accumulation.

180 is results from impairment of the ability of AID to access the IgV genes due to reduced formation of

181 of overlapping AGCT hotspots, the absence of AID cold spots, and an abundance of polymerase eta hotsp

182 The access of AID to the nucleus is limited by CRM1-mediated nuclear e

183 ism to limit the tumor promoting activity of AID when it overwhelms uracil excision repair.

184 study highlights the broad applicability of AID for functional analysis of proteins across the Plasm

185 Application of AID to the calcium-regulated protein phosphatase, calcin

186 Our results elucidate the molecular basis of AID cytoplasmic retention, define its functional relevan

187 uses or retrotransposons and, in the case of AID, changing antibody sequences to drive affinity matur

188 esidue in the putative RNA-binding domain of AID impairs recruitment of AID to S region DNA, thereby

189 We propose that the downregulation of AID in aged human B cells may occur through binding of m

190 e presence of factors required downstream of AID binding to effect SHM.

191 extent ibrutinib, enhanced the expression of AID and increased somatic hypermutation and chromosomal

192 uting to the observed aberrant expression of AID in these patients.

193 d elevation in RAG1 while high expression of AID marked pre-B-ALL lacking common cytogenetic changes.

194 and recurrent lesions reflect the extent of AID-mediated DNA damage and selection.

195 portantly, the reduction in the formation of AID-accessible ssDNA in cells lacking H3.3 is independen

196 tors or ibrutinib increased the formation of AID-dependent tumours in pristane-treated mice.

197 133 MCL cases; assessed the functionality of AID by evaluating in vivo class switch recombination in

198 ines to the other three bases independent of AID hotspot motifs, generating a large repertoire of var

199 nfected primary B cells for the induction of AID mRNA and protein.

200 ivated by functional EBNA3C and induction of AID.

201 We find that the interactions of AID with eEF1A and heat-shock protein 90 kD (HSP90) are

202 on of RNA lariat processing leads to loss of AID localization to S regions and compromises CSR; both

203 Mechanisms of AID targeting and catalysis remain elusive despite its c

204 at these features are universal mediators of AID recruitment.

205 nce of G4 recognition and oligomerization of AID in CSR.

206 Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartil

207 , our data implicate intrinsic preference of AID for structured substrates and uncover the importance

208 We also analyzed the presence of AID hotspots and coldspots at different points in lineag

209 attributable to a differential processing of AID-initiated lesions in distinct B cell populations.

210 e investigated the biochemical properties of AID from a sea lamprey, nurse shark, tetraodon, and coel

211 binding domain of AID impairs recruitment of AID to S region DNA, thereby abolishing CSR.

212 Central to the recruitment of AID to the IgV genes are factors that regulate the gener

213 of miR-155 to the 3'-untranslated regions of AID mRNA and/or binding of miR-16 to the 3'-untranslated

214 em into a model for multilevel regulation of AID expression and targeting in immunoglobulin and non-i

215 proteins contribute to optimal resolution of AID-induced DSBs.

216 T in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation rem

217 ith data in the murine context, silencing of AID in human bone marrow cells skews differentiation tow

218 ently, we solved the functional structure of AID and demonstrated that these properties are due to no

219 nded DNA (ssDNA), the enzymatic substrate of AID Here, we report that chicken DT40 cells lacking vari

220 that telomeres are off-target substrates of AID and that B cell proliferation depends on protective

221 Targeting of AID to antibody variable (V) regions results in somatic

222 Preferential targeting of AID-mediated DSBs to S sequences is critical for allowin

223 However, the downstream targets of AID action mediating neuroprotection remained so far unk

224 and SHM are regulated by phosphorylation on AID serine38 (pS38), but the role of pS38 in off-target

225 , we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS,

226 We created a novel Pan1-degron allele, Pan1-AID, in which Pan1 can be specifically and efficiently d

227 , Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to

228 In a large population with primary AID, azathioprine exposure was associated with a 7-fold

229 uggest a role for the HMT MMSET in promoting AID-mediated DNA breaks during CSR.

230 ature B cell cancers by eliciting protracted AID expression in GC B cells.

231 by which variable and switch regions recruit AID essentially is the same but that the two regions dif

232 These results suggest that Sox2 may regulate AID expression in class-switched B cells to suppress gen

233 rally highly toxic, mechanisms that regulate AID expression are of much relevance to CSR and genomic

234 exon sequences and their ability to regulate AID deamination and subsequent repair process.

235 equence-intrinsic properties, which regulate AID deamination and affect the preferential access of do

236 s switching is in part due to CDK2-regulated AID nuclear access at the G1/S border.

237 Altering the timing of cell cycle-regulated AID nuclear residence increases DNA damage at off-target

238 3-kinase delta (PI3Kdelta) pathway regulates AID by suppressing its expression in B cells.

239 However, precise mechanisms regulating AID deamination frequency remain incompletely understood

240 tinguish it from other mechanisms regulating AID.

241 ing to an arginine to histidine replacement (AID(R112H)).

242 chemical and structural approaches to report AID-preferred nucleic acid substrates, illuminating AID

243 Second, AID mutates targets in diverse non-Ig passengers in GC B

244 on frequency to the Igh locus and to several AID off-target sites.

245 age to the B-cell genome during CSR and SHM, AID induces unwanted (and sometimes oncogenic) mutations

246 king the Mlp1/2 nuclear basket proteins show AID-dependent genomic instability and replication defect

247 l knockout mouse strain with the GC-specific AID-Cre transgenic strain.

248 Despite both interactions stabilizing AID, the nature of the AID fractions associated with HSP

249 we have developed an in vivo assay to study AID targeting of passenger sequences replacing a V exon.

250 Here, we study AID-mediated lesions in the context of nuclear architect

251 pment independently of UV damage and suggest AID as a potential target for skin cancer therapeutics.

252 ll development, Blimp1 will in turn suppress AID expression and drive the formation of IgG-secreting

253 Although off-target AID activity also contributes to oncogenic point mutatio

254 Off-target AID association also occurs, which causes oncogenic muta

255 new insights into the mechanisms that target AID activity to specific genomic regions, revealing an i

256 intronic switch RNA acts in trans to target AID to S region DNA.

257 Thus, targeted AID-mediated mutagenesis (TAM) provides a forward geneti

258 cover an RNA-mediated mechanism of targeting AID to DNA.

259 That AID alone can track along with RNAP during transcription

260 We demonstrated that AID and RAG1-RAG2 drove leukemic clonal evolution with r

261 Finally, we demonstrated that AID mutations caused hyperactive Set2 in vivo and displa

262 We show here that AID deficiency in mice enables suppression of allograft

263 These results indicate that AID and TET2 share common effects on myeloid and erythro

264 We propose that AID could be a novel molecular target for controlling an

265 We propose that AID-induced damage at telomeres acts as a fail-safe mech

266 We report that AID enzymes were produced in a discrete population of im

267 Recent studies have revealed that AID's DNA mutator activity is regulated by the RNA exoso

268 Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirec

269 Here, we show that AID is transiently in spatial contact with genomic DNA f

270 other types of human cancer, suggesting that AID-mediated, CpG-methylation dependent mutagenesis is a

271 The AID / APOBEC genes are a family of cytidine deaminases t

272 The AID deficiency inhibits DSA-mediated AV after aorta tran

273 The AID full-length transcript and the most frequent splice

274 The AID(-/-) splenocytes were comparable to wild type spleno

275 The AID/APOBEC family enzymes convert cytosines in single-st

276 s in the orthologous gene in humans, and the AID(R112H) mutation is frequently found in HIGM patients

277 tic modification approach has identified the AID/RAD51 axis as a target for a potentially clinically

278 Beyond insights into the AID-DNA interface, our Sat-Sel-Seq approach also serves

279 he CBD common to all isoforms, but lacks the AID.

280 eractions stabilizing AID, the nature of the AID fractions associated with HSP90 or eEF1A are differe

281 and it was shown that transactivation of the AID gene (AICDA) is associated with EBNA3C binding to hi

282 activity of APOBEC3B (A3B), a member of the AID/APOBEC family of cytidine deaminases.

283 t is based on the activity of members of the AID/APOBEC family of deaminases.

284 Together, our results demonstrate that the AID system provides a powerful new tool for spatiotempor

285 aminates cytosines in DNA and belongs to the AID/APOBEC family of enzymes.

286 APOBEC3G (A3G) belongs to the AID/APOBEC protein family of cytidine deaminases (CDA) t

287 t amino acid sequence divergence among these AID orthologs is predicted to manifest as notable struct

288 Thus, AID activity can be differentially targeted by phosphory

289 e in BER and could potentially contribute to AID-initiated antibody diversification through this acti

290 smatch repair or uracil glycosylase (UNG) to AID-initiated U:G mismatches.

291 letely reconstituted by expressing wild-type AID.

292 cript and the most frequent splice variants (AID-DeltaE4a, AID-DeltaE) were detected in 128 (96.2%),

293 Whereas AID levels were not altered in Id3-depleted activated B

294 iption bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, ye

295 The mechanism by which AID is recruited to V genes and S region DNA is poorly u

296 (SHM) in B cells, but the mechanism by which AID prevents the accumulation of autoreactive B cells in

297 lated B cells and negatively associated with AID in the same B cells after stimulation with CpG.

298 Consistent with AID, comparable somatic hypermutation frequencies and cl

299 ammalian genes, suggesting co-evolution with AID / APOBECs may have had an impact on the genomes of t

300 hibiting eEF1A prevents the interaction with AID, which accumulates in the nucleus and increases clas

301 munomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm.