ライフサイエンスコーパス: V(D)J recombination

1 sity (D), and joining (J) subgenic elements (V(D)J recombination).

2 which is required for rejoining DSBs during VDJ recombination.

3 epair of DNA double-strand breaks (DSBs) and V(D)J recombination.

4 g an unexpected role for RAG proteins beyond V(D)J recombination.

5 AG1) and RAG2 result in loss or reduction of V(D)J recombination.

6 rk that regulates B cell fate by controlling V(D)J recombination.

7 y chain (IgH) gene locus prior to and during V(D)J recombination.

8 ect consequences of BCL11A/RAG modulation on V(D)J recombination.

9 lation of antigen receptor gene assembly via V(D)J recombination.

10 en receptor variable region gene segments by V(D)J recombination.

11 ased on lymphocyte Ag receptors generated by V(D)J recombination.

12 and breaks created by ionizing radiation and V(D)J recombination.

13 ted activation of germline transcription and V(D)J recombination.

14 cleavage activity, is required for efficient V(D)J recombination.

15 rk that regulates B cell fate by controlling V(D)J recombination.

16 y impaired DNA damage responses or defective V(D)J recombination.

17 hich plays essential roles in DNA repair and V(D)J recombination.

18 napse and end-joining at modest level during V(D)J recombination.

19 rotein(s) to limit error-prone repair during V(D)J recombination.

20 ne lymphocytes show no measurable defects in V(D)J recombination.

21 g lymphocyte Ag receptor loci cleaved during V(D)J recombination.

22 2+) are present, unlike a single nick during V(D)J recombination.

23 re defects in end joining during chromosomal V(D)J recombination.

24 sites is dispensable for the joining step of V(D)J recombination.

25 sequences may have a role in long-range IgH V(D)J recombination.

26 ring proper repair of DNA breaks made during V(D)J recombination.

27 transcriptional accessibility helps control V(D)J recombination.

28 lopment and their lymphocytes support normal V(D)J recombination.

29 pening step, which is crucial and unique for V(D)J recombination.

30 D cluster and thereby influence targeting of V(D)J recombination.

31 NHEJ) repair pathway and plays a key role in V(D)J recombination.

32 ce interactions between gene segments during V(D)J recombination.

33 equires an intact thymic epithelium, but not V(D)J recombination.

34 ne 4 (H3K4me3), and in some manner increases V(D)J recombination.

35 antigen receptor locus translocations during V(D)J recombination.

36 insights into the mechanism of physiological V(D)J recombination.

37 nerating diversity of lymphocyte AgRs during V(D)J recombination.

38 phenotypes that are suggestive of defects in V(D)J recombination.

39 of antigen receptor genes by the process of V(D)J recombination.

40 y and caused by defects in lymphoid-specific V(D)J recombination.

41 T-cell development and T-cell receptor (TCR) V(D)J recombination.

42 hairpin intermediates that are formed during V(D)J recombination.

43 re, we aimed to study the role of XLF during V(D)J recombination.

44 double-strand breaks (DSBs) generated during V(D)J recombination.

45 teins participate in the DNA repair phase of V(D)J recombination.

46 tions, play a fundamental role in regulating V(D)J recombination.

47 ect consequences of BCL11A/RAG modulation on V(D)J recombination.

48 te asymmetry important for the 12/23 rule of V(D)J recombination.

49 ucial for DNA double-strand break repair and V(D)J recombination.

50 A rearrangements in lymphoid cells, known as V(D)J recombination.

51 defect in DNA double-strand break repair and V(D)J recombination.

52 omplex that reflects the known 12/23 rule of V(D)J recombination.

53 ional levels to facilitate their assembly by V(D)J recombination.

54 lectively called variable-diversity-joining (V(D)J) recombination.

55 rated during Variable, Diverse, and Joining [V(D)J] recombination.

56 inetics of variable, diversity, and joining [V(D)J] recombination.

57 ly susceptible to transforming events due to V(D)J recombination, a high rate of cellular turnover an

58 Therefore, V(D)J recombination, a physiological DNA rearrangement p

59 lyze site-specific DNA cleavage reactions in V(D)J recombination, a process that assembles antigen re

60 RAG1 and RAG2 mediate VDJ recombination, a process necessary for the maturatio

61 es (Tcra, Tcrb, Tcrg, Tcrd) are assembled by V(D)J recombination according to distinct programs durin

62 DSBs) induced by the RAG endonuclease during V(D)J recombination activate the Ataxia Telangiectasia m

63 utation that impairs, but does not abrogate, V(D)J recombination activity.

64 a significant role in governing the level of V(D)J recombination activity.

65 fferential activation of component parts for V(D)J recombination, allelic exclusion, and receptor edi

66 in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival.

67 gnals creates an ectopic hub of RAG-mediated V(D)J recombination and chromosomal translocations.

68 tion and associated molecular events such as V(D)J recombination and class switch recombination.

69 decrease in the fitness of cells undergoing V(D)J recombination and CSR.

70 ng' process, which can also lead to Iglambda V(D)J recombination and expression, provides a mechanism

71 ion within the Ig heavy chain locus precedes V(D)J recombination and has been proposed to be associat

72 clease that opens coding hairpin ends during V(D)J recombination and has critical roles in postirradi

73 ) mediates double-stranded DNA break repair, V(D)J recombination and immunoglobulin class switch reco

74 ATM is important for V(D)J recombination and immunoglobulin class-switch reco

75 TEMIS C terminus is dispensable for cellular V(D)J recombination and in vitro nuclease assays with C-

76 Although NHEJ is required for V(D)J recombination and lymphocyte development, XLF-defi

77 C)) exhibit lymphopenia, reflecting impaired V(D)J recombination and lymphocyte development.

78 intains genome stability and is required for V(D)J recombination and lymphocyte development.

79 However, ATM deficiency causes only modest V(D)J recombination and lymphocyte developmental defects

80 ted pro-B lines abrogates DSB joining during V(D)J recombination and sensitizes the cells to ionizing

81 We find that APE2 is not required for V(D)J recombination and that the turnover rate of APE2-d

82 y different recombination reactions, such as V(D)J recombination and transposition.

83 harbour intermediates indicative of ongoing V(D)J recombination and which contain cells with pro-B,

84 mmed mechanistic feature of CSR as it is for V(D)J recombination and, if so, how this is achieved is

85 mphopenia associated with a severe defect in V(D)J recombination and, in the absence of p53, increase

86 uman IGHV1-2( *)02 segment to undergo normal V(D)J recombination and, thereby, leads to the generatio

87 Variable, diversity and joining (V(D)J) recombination and immunoglobulin class switch rec

88 created during variable (diversity) joining [V(D)J] recombination and class switch recombination (CSR

89 data provide a window into the mechanisms of VDJ recombination and diversity creation and allow us to

90 Mutations impairing VDJ recombination and DNA repair were the most common un

91 This mechanism promotes VDJ recombination and effective selection of cells expre

92 ficant correlation between biases induced by VDJ recombination and our inferred selection factors tog

93 B ligation, resulting in failure to complete VDJ recombination and subsequent block of B-lymphocyte m

94 nteraction with Ligase IV or DNA-PKcs reduce V(D)J recombination, and Artemis mutations that affect i

95 Shark Ag receptors are generated through V(D)J recombination, and because it is a mechanism known

96 ow peripheral B cells that attempt secondary V(D)J recombination, and determine a role for mechanisti

97 ns involving the Tcralpha/delta locus during V(D)J recombination, and instead harbor alterations at t

98 In mice, C-NHEJ, V(D)J recombination, and lymphocyte development are, at

99 deficiency in mice severely impairs C-NHEJ, V(D)J recombination, and lymphocyte development while al

100 features of "open" chromatin correlate with V(D)J recombination, and promoters and enhancers have be

101 ouble-strand breaks (DSBs) during Tcra locus V(D)J recombination, and to require the Tcra enhancer (E

102 e to state in a hidden Markov model (HMM) of VDJ recombination, and assumed that mutations occur via

103 a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement,

104 combinatorial splicing of coding segments by V(D)J recombination are hallmarks of vertebrate immunity

105 Moreover, these defects in V(D)J recombination are remarkably similar to those obse

106 Ig gene locus contraction and looping during V(D)J-recombination are essential for creating a diverse

107 ntroduced by somatic mutation or heavy chain VDJ recombination are necessary and sufficient for Dsg3

108 for understanding retroviral integration and V(D)J recombination as well as many other DNA transposit

109 eristic of early thymocyte precursors before V(D)J recombination, as the most robust predictor of ind

110 nd in increased ARTEMIS activity in cellular V(D)J recombination assays.

111 V(D)J recombination assembles Ag receptor genes during l

112 V(D)J recombination assembles antigen receptor genes in

113 V(D)J recombination assembles immunoglobulin and T cell

114 e RAG postcleavage complex normally prevents V(D)J recombination-associated DSBs from accessing alter

115 We propose that dicentrics formed by joining V(D)J recombination-associated IgH DSBs to DSBs downstre

116 ed NHEJ-deficient splenic B cells accumulate V(D)J-recombination-associated breaks at the lambda IgL

117 iversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of develop

118 protein complex is known to be essential for V(D)J recombination at Ag receptor loci in vivo.

119 by the CCCTC binding factor (CTCF) regulates V(D)J recombination at Ag receptor loci.

120 The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also bi

121 Enhancers at AR loci are known to control V(D)J recombination at associated alleles, in part by in

122 within chromatin to target specific loci for V(D)J recombination at different stages of lymphoid deve

123 tify the genomic instability associated with V(D)J recombination at the TCRdelta locus as the molecul

124 uggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tc

125 During V(D)J recombination, ATM and DNA-PKcs have unique functi

126 The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombi

127 her with its cofactor RAG2, is essential for V(D)J recombination but is a potent threat to genome sta

128 s because of its requirement, not in NHEJ or V(D)J recombination, but in telomere maintenance.

129 ic DNA insertions by transposition and trans-V(D)J recombination, but only few such putative events h

130 es in processing and joining DNA ends during V(D)J recombination, but that these roles have been mask

131 ation-activating gene endonuclease initiates V(D)J recombination by cleaving a pair of gene segments

132 one might play a critical regulatory role in V(D)J recombination by enhancing DNA binding and enzymat

133 pe long-range interactions and contribute to V(D)J recombination by facilitating lineage- and develop

134 ation activating gene endonuclease initiates V(D)J recombination by generating DSBs between two V(D)J

135 The RAG1/2 endonuclease initiates V(D)J recombination by introducing DNA double-strand bre

136 The RAG proteins initiate V(D)J recombination by mediating synapsis and cleavage o

137 ropose that recombination centers coordinate V(D)J recombination by providing discrete sites within w

138 Conversely, we report low levels of V(D)J recombination by RAG1 in the absence of RAG2.

139 We conclude that CTCF can regulate V(D)J recombination by segregating RSSs into distinct lo

140 Our results suggest that V(D)J recombination can be regulated by AMPK activation,

141 Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell devel

142 the lack of variable, diversity and joining [V(D)J] recombination completely abolishes the Tcralpha/d

143 orting that E2A, PAX5, and the RAGs are in a VDJ recombination complex bound to key sequences on the

144 We show that pre-BCR activation releases the VDJ recombination complex through calmodulin binding to

145 Our studies elucidate a long-sought Igh V(D)J recombination control region and indicate a new ro

146 Initiation of V(D)J recombination critically relies on the formation o

147 includes overexpression of genes involved in VDJ recombination, CXCR4 pathway signaling, and BCL2 fam

148 CD8(+) thymocytes, but led to no discernible V(D)J recombination defect in G1 phase cells beyond that

149 vation in XLF-deficient pro-B lines leads to V(D)J recombination defects associated with marked degra

150 icient patients in the absence of measurable V(D)J recombination defects.

151 n horses and dogs that result in deficits in V(D)J recombination, DNA repair, and SCID.

152 on of a CBE-based IgH locus element disrupts V(D)J recombination domains and, correspondingly, alters

153 an inability to process and join chromosomal V(D)J recombination DSB intermediates.

154 trict requirement for classical NHEJ to join V(D)J recombination DSB intermediates.

155 o find that PAXX deficiency has no impact on V(D)J recombination DSB joining in ATM-deficient pro-B l

156 report that PAXX is dispensable for joining V(D)J recombination DSBs in G1-arrested mouse pro-B-cell

157 As V(D)J recombination DSBs occur in developing progenitor

158 ent for NHEJ to resolve DSBs associated with V(D)J recombination, DSBs associated with CSR can be res

159 ating gene products, RAG1 and RAG2, initiate V(D)J recombination during lymphocyte development by cle

160 Feedback inhibition of V(D)J recombination enforces Ag receptor allelic exclusi

161 V(D)J recombination entails double-stranded DNA cleavage

162 ned XLF and H2AX deficiency severely impairs V(D)J recombination, even though H2AX deficiency alone h

163 Regulation of V(D)J recombination events at immunoglobulin (Ig) and T-

164 region exons are assembled by RAG-initiated V(D)J recombination events in developing gammadelta thym

165 nerally believed to result from illegitimate V(D)J recombination events.

166 ssion levels of several transcripts encoding V(D)J recombination factors were decreased in adults as

167 n initial random DNA editing process, called VDJ recombination, followed by functional selection of c

168 SJ defects, indicating that the overlapping V(D)J recombination functions of ATM and DNA-PKcs are me

169 thy humans suggests an important role of the V(D)J recombination-generated junctional and allele-spec

170 damage-induced cell death, however, because V(D)J recombination generates double-strand breaks and m

171 es showed greatly enhanced expression of the VDJ recombination genes DNTT, RAG1, and RAG2, but not AI

172 role for the C-terminal region of Artemis in V(D)J recombination has not been defined, despite the pr

173 -established functions in the DNA repair and V(D)J recombination, hence loss of DNA-PK leads to sever

174 development, XLF-deficient mice have normal V(D)J recombination, highlighting the need for an altern

175 V(D)J recombination in B and T cells is required for the

176 apamycin induces rag expression and promotes V(D)J recombination in B cells.

177 ates RAG-mediated cleavage and repair during V(D)J recombination in CD4(+) CD8(+) DP thymocytes.

178 netic locus (Tcra/Tcrd locus) that undergoes V(D)J recombination in CD4(-)CD8(-) double-negative (DN)

179 shows that XLF has an important role during V(D)J recombination in creating diversity of the reperto

180 and resolves the DSBs generated during both V(D)J recombination in developing lymphocytes and class

181 RAG initiates antibody V(D)J recombination in developing lymphocytes by generat

182 ntial role in adaptive immunity by mediating V(D)J recombination in developing lymphocytes.

183 r and Ig gene segments that are required for V(D)J recombination in developing lymphocytes.

184 ination by RAG1 alone differs from canonical V(D)J recombination in having lost the requirement for a

185 tigen receptors, which are generated through V(D)J recombination in lymphoid precursors.

186 ctor (XLF) C-NHEJ protein is dispensable for V(D)J recombination in normal cells, but because of func

187 equired for efficient class switch (CSR) and V(D)J recombination in part because they protect DNA end

188 However, the occurrence of V(D)J recombination in peripheral B cells is controversi

189 V(D)J recombination in progenitor B (pro-B) cells assemb

190 he V(H)-to-D intergenic region regulates Igh V(D)J recombination in the contexts of developmental ord

191 V(D)J recombination in the vertebrate immune system gene

192 nstream targets in the cell-cycle control of V(D)J recombination in vivo.

193 icient lymphocytes, despite moderate role in V(D)J recombination in WT cells.

194 ubstrate histone H2AX are both essential for V(D)J recombination in XLF-deficient lymphocytes, despit

195 signaling in B-cell development, we studied VDJ recombination in the pro-B cells of FLT3/ITD mice an

196 y and are not required for extra-chromosomal V(D)J recombination, indicating a role for chromatin-ass

197 nt translocations and amplifications involve V(D)J recombination-initiated breaks in the Tcrd locus,

198 mutant mice harbor translocations that fuse V(D)J recombination-initiated IgH double-strand breaks (

199 is dispensable for pro-B-cell lymphomas with V(D)J recombination-initiated translocations, but is req

200 tions during lymphocyte development, joining V(D)J recombination intermediates during antigen recepto

201 ase with zebrafish maturity, suggesting that VDJ recombination involves a level of deterministic prog

202 In these contexts, V(D)J recombination is controlled by modulating substrat

203 V(D)J recombination is essential for the maturation of l

204 V(D)J recombination is initiated by RAG1 and RAG2, which

205 V(D)J recombination is initiated by the binding of the R

206 V(D)J recombination is initiated by the RAG endonuclease

207 V(D)J recombination is initiated by the recombination-ac

208 f the accessibility model, which states that V(D)J recombination is regulated by controlling the abil

209 Within the 2.7-megabase mouse Igh locus, V(D)J recombination is regulated to ensure specific and

210 To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphe

211 ously in double-negative thymocytes and that V(D)J recombination is suppressed on peripheral as compa

212 V(D)J recombination is the distinguishing feature of ada

213 The first step in V(D)J recombination is the formation of specific DNA dou

214 Here, we show that V(D)J recombination is unaffected by the complete absenc

215 This process, known as "VDJ recombination", is implemented via a series of stoch

216 CTCF-mediated looping was shown to influence V(D)J recombination, it was not possible to fully resolv

217 domain and, correspondingly, shifts the Tcrd V(D)J recombination landscape by leading to predominant

218 combined DNA-PKcs and ATM deficiency during V(D)J recombination leads to accumulation of unjoined SE

219 Despite the central role of the PC in V(D)J recombination, little is understood about its stru

220 her, these data suggest a mechanism by which V(D)J recombination may feed back to regulate local Dbet

221 years that the variable (diversity) joining [V(D)J] recombination-mediated assembly of diverse B and

222 We show that during V(D)J recombination, MRN deficiency leads to the aberran

223 ll development, RAG-dependent DNA breaks and V(D)J recombination occur at three T-cell receptor (TCR)

224 V(D)J recombination occurs during the antigen-independen

225 precisely at differentiation stages in which V(D)J recombination occurs.

226 V(D)J recombination of antigen receptor gene segments in

227 c repeat (CRISPR) loci in prokaryotes and by V(D)J recombination of immunoglobulin genes in vertebrat

228 V(D)J recombination of TCR loci is regulated by chromati

229 Lucas et al. report the visualization of V(D)J recombination of the immunoglobulin heavy-chain ge

230 e discuss CTCF function in the regulation of V(D)J recombination on the basis of established knowledg

231 V(D)J recombination only occurs between V, D, and J segm

232 Errors in either V(D)J recombination or CSR can initiate chromosomal tran

233 nome instability, has only modest effects on V(D)J recombination or lymphocyte development.

234 ning region (CDR3) of the ANA originate from V(D)J recombination or somatic hypermutation (SHM) is no

235 In addition to its role in VDJ recombination, our study points out that the full-le

236 We found that, despite defective V(D)J recombination, P1(-/-)/D(-/-) lymphomas lacked clo

237 F protein is not required for the process of V(D)J recombination per se, CTCF turned out to be essent

238 ly resolve the relative contributions to the V(D)J recombination phenotype of changes in accessibilit

239 the impact of heritable factors on both the V(D)J recombination process and on thymic selection.

240 d participates in hairpin opening during the V(D)J recombination process and repair of a subset of DN

241 tes are assembled from gene fragments by the V(D)J recombination process.

242 velopment of T and B cells by initiating the VDJ recombination process that leads to generation of a

243 fferent ages, we quantify the changes in the VDJ recombination process that occur from embryo to youn

244 nts can induce specific abnormalities of the VDJ recombination process.

245 cal impact of selection on the output of the VDJ recombination process.

246 During V(D)J recombination, RAG targeting to correct sites vers

247 transposition pathway resembles that of the V(D)J recombination reaction and the mechanism of hAT an

248 g DSB intermediates of the G1 phase-specific V(D)J recombination reaction in progenitor lymphocytes.

249 e RAG1/RAG2 endonuclease (RAG) initiates the V(D)J recombination reaction that assembles immunoglobul

250 This process is executed by the V(D)J recombination reaction, which can be divided into

251 al lamina propria (LP), where the associated V(D)J recombination/receptor editing processes modulate

252 During V(D)J recombination, recombination activating gene (RAG)

253 During V(D)J recombination, recombination activating gene prote

254 Here we report in mice a key Igh V(D)J recombination regulatory region, termed intergenic

255 ultifunctional phospho-protein with roles in V(D)J recombination, repair of double-strand breaks by n

256 , our previous analysis of mice containing a V(D)J recombination reporter inserted into Vbeta14 (Vbet

257 Immunoglobulin heavy-chain locus V(D)J recombination requires a 3D chromatin organization

258 Antigen receptor locus V(D)J recombination requires interactions between widely

259 lexes support cleavage activity regulated by V(D)J recombination's '12/23 rule' and exhibit plasticit

260 ciency in Artemis is associated with lack of V(D)J recombination, sensitivity to radiation and radiom

261 rd, including sequential rearrangements from V(D)J recombination signal sequence fusions.

262 terminal inverted repeats (TIRs) resembling V(D)J recombination signal sequences.

263 versification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class sw

264 for coding join formation within chromosomal V(D)J recombination substrates.

265 V(D)J recombination takes place during lymphocyte develo

266 ay distinct from DNA transposition and trans-V(D)J recombination that destabilizes the genome and sha

267 developed approach for studying chromosomal V(D)J recombination that has been modified to allow for

268 immature B cells, allowing continued Igkappa V(D)J recombination that replaces the initial VkappaJkap

269 ginates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gen

270 of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate

271 ing gene 1 (RAG1) and RAG2 proteins initiate V(D)J recombination, the process that assembles the B- a

272 is essential in vertebrates because, during V(D)J recombination, the RAG complex generates hairpins

273 During V(D)J recombination, the RAG1/2 recombinase is thought t

274 Produced through V(D)J recombination, this loop is quite diverse, with di

275 the C-terminal region of Artemis influences V(D)J recombination through its interaction with both Li

276 Developing B lymphocytes undergo V(D)J recombination to assemble germ-line V, D, and J ge

277 sistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive

278 ates that possess an immune system utilizing V(D)J recombination to generate Ag receptors.

279 The ability of V(D)J recombination to generate vast primary B-cell repe

280 RAG-2 enzyme upon entry to S phase restricts V(D)J recombination to the G0-G1 phase of the cell cycle

281 in (Ig)-superfamily of genes; and instead of V(D)J recombination VLR are somatically assembled by a g

282 d RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution

283 Defective V(D)J recombination was complemented by wild-type ARTEMI

284 V(D)J recombination was preserved in NIR-deficient DN3 d

285 ms by which CTCF-mediated looping can impact V(D)J recombination, we introduced an ectopic CTCF bindi

286 tructural information on the early stages of V(D)J recombination, we isolated a complex of the core R

287 To clarify the role of the RR in V(D)J recombination, we totally deleted it in the mouse

288 RAG1-like, have a latent ability to initiate V(D)J recombination when coexpressed with RAG2 and that

289 The first occurs during VDJ recombination, when inverted DH genes are usually av

290 upstream of Cmu, have important roles during V(D)J recombination, whereas there is no clue about a ro

291 ch developing lymphocyte by a process called V(D)J recombination, which assembles specific, independe

292 In contrast to V(D)J recombination, which is almost exclusively depende

293 gene assembly occurs through the process of V(D)J recombination, which is initiated when the RAG end

294 ing the lymphoid-specific DNA rearrangement, V(D)J recombination, which is required for lymphocyte de

295 that catalyzes specific DNA cleavage during V(D)J recombination, which is required for the assembly

296 oping lymphocytes, DSBs are generated during V(D)J recombination, which is required to assemble the s

297 tor repertoire is sculpted by the process of V(D)J recombination, which must strike a balance between

298 the core-enhancer Emu element mainly affects VDJ recombination with minor effects on class switch rec

299 Despite a severe defect in VDJ recombination with partial blockade at the pro-B cel

300 n genetic and molecular features of NHEJ and V(D)J recombination within cells.