ライフサイエンスコーパス: CSR

1 CSR and SHM are regulated by phosphorylation on AID seri

2 CSR and SHM require the essential activity of the DNA ac

3 CSR creates a virtually unique IgH locus in every B cell

4 CSR for 6 d was sufficient to impair BBB structure and f

5 CSR has been previously linked to proliferation, and in

6 CSR is preceded by inducible germline (GL) transcription

7 CSR not only diminished endothelial and inducible nitric

8 CSR occurs via an intrachromosomal looping out and delet

9 CSR rates were lower in mTOR KI and KO mice, and pharmac

10 CSR-1 is a germline-expressed C. elegans Argonaute prote

11 CSR-activated B lymphocytes generate multiple S-region D

12 o IgA results in reduced, but not abolished, CSR.

13 t of AID to S region DNA, thereby abolishing CSR.

14 To achieve CSR that mimics a common pattern of human sleep loss, we

15 ping and resting splenic B cells and altered CSR in activated B cells.

16 Ss, and sustained over the course of AID and CSR induction.

17 nt pS38 abated AID chromatin association and CSR but not mutation at Myc.

18 role for APE1 in switch region cleavage and CSR.

19 B cells severely inhibits AID expression and CSR, whereas deletion of Sox2 increases the frequency of

20 t MR imaging, SII signal intensity index and CSR chemical-shift ratio have high accuracy to distingui

21 worsening heart failure varied with LVEF and CSR.

22 cluding BASELINe), clonality (Change-O), and CSR.

23 By linking cell proliferation and CSR, c-Myc is thus a critical component for a potent imm

24 of cells undergoing V(D)J recombination and CSR.

25 line, DSB formation is severely reduced and CSR frequency is impaired.

26 Although SHM and CSR are fundamentally different, their independent roles

27 generates deletions, indicating that SHM and CSR employ the same mechanism.

28 RGalaxy includes the newly developed SHM and CSR pipeline to analyze SHM and/or CSR in BCR rearrangem

29 ine the independent contributions of SHM and CSR to the generation and persistence of memory in the a

30 mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can ac

31 ossible role for the FANC pathway in SHM and CSR, we analyzed both processes in B cells derived from

32 und that PTIP functions in transcription and CSR separately from its association with the MLL3/MLL4 c

33 of sterile gamma1 germ-line transcripts and CSR to IgG1.

34 homologous recombination that can antagonize CSR.

35 hat encapsulates Curated Short Read archive (CSR) and a proteome-wide variation effect analysis tool

36 elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin,

37 the cause of these abnormalities, we assayed CSR in Lig4(R/R) B cells generated via preassembled IgH

38 To better quantify performance during both CSR and TSD, we developed a unified mathematical model t

39 C. briggsae CSR-1-associated small RNAs that we identified by immuno

40 cellent (intraclass correlation coefficient: CSR chemical-shift ratio , 0.893; SII signal intensity i

41 cognition or oligomerization both compromise CSR in splenic B cells.

42 ID localization to S regions and compromises CSR; both defects can be rescued by exogenous expression

43 Defective CSR was linked to failed NHEJ and residual A-EJ access t

44 tion of Med1 in B cells results in defective CSR and reduced acceptor S region transcription.

45 Finally, AT deficiency resulted in defective CSR to distal constant regions that might reflect an imp

46 These results suggest that defective CSR caused by MMSET deficiency could be a cause of Ab de

47 globulin class-switch recombination defects (CSR-D) are rare primary immunodeficiencies characterized

48 hanism by which 53BP1 facilitates deletional CSR and inhibits inversional switching events remains un

49 he link with 53BP1 enforcement of deletional CSR.

50 that is capable of robust cytokine-dependent CSR to IgA results in reduced, but not abolished, CSR.

51 Despite CSR-1 being preserved among diverse nematodes, the conse

52 gage in germline transcription and determine CSR targeting.

53 lus tumor bed (TB) boost (n=9), reduced-dose CSR plus PF boost (n=28), or reduced-dose CSR plus TB bo

54 se CSR plus PF boost (n=28), or reduced-dose CSR plus TB boost (n=23), with or without chemotherapy.

55 Patients treated with reduced-dose CSR plus TB boost showed stable intellectual trajectorie

56 erior fossa (PF) boost (n=51), standard-dose CSR plus tumor bed (TB) boost (n=9), reduced-dose CSR pl

57 ients were treated with either standard-dose CSR with a posterior fossa (PF) boost (n=51), standard-d

58 or S region at sufficient frequency to drive CSR in a large fraction of activated B cells.

59 During CSR, AID instigates DNA double-strand break (DSB) format

60 During CSR, DSBs are produced in the G1 phase of the cell cycle

61 During CSR, the IgH locus undergoes dynamic three-dimensional s

62 in promoting AID-mediated DNA breaks during CSR.

63 mote repair and recombination of DSBs during CSR, we examined whether mouse splenic B cells deficient

64 anner in resolving switch region DSBs during CSR.

65 egion DNA double-strand breaks (DSBs) during CSR, and it is not required for SHM.

66 S regions and the IgH locus enhancers during CSR and their transcriptional activation.

67 the emergent functions of RNA exosome during CSR, SHM, and other chromosomal alterations in B cells,

68 the Ig gene, the mismatches generated during CSR are processed to create double-stranded breaks (DSBs

69 ollateral damage to the B-cell genome during CSR and SHM, AID induces unwanted (and sometimes oncogen

70 affecting 53BP1 and gammaH2AX levels during CSR.

71 o the Smu-Cmu region of the IgH locus during CSR and that knockdown of cohesin or its regulatory subu

72 illuminating AID targeting mechanisms during CSR and SHM.

73 Bs generated by ionizing radiation or during CSR are hyperresected in the absence of RIF1.

74 nces the choice of DSB repair pathway during CSR.

75 vity at downstream acceptor S regions during CSR and that in atm(-/-) cells Smu DSBs accumulate as th

76 us enhancers and the acceptor regions during CSR and that their knockdown in CH12 cells results in im

77 a link between DNA damage and repair during CSR.

78 in splenic B cells, Fanca is required during CSR to stabilize duplexes between pairs of short microho

79 MLL4 complex to mediate transcription during CSR.

80 witch regions do not appear to affect either CSR or R-loop elongation, whereas a longer (150 bp) inse

81 B cell-specific PTEN overexpression enhances CSR.

82 tensity index and 100%, 96.7%, and 0.849 for CSR chemical-shift ratio .

83 ouse and human B lineage cells activated for CSR or SHM, we report that most robust AID off-target tr

84 ent tonsils exhibited varying capacities for CSR to IgE ex vivo.

85 deaminase (AID) to S regions is critical for CSR; however, the underlying mechanism has not been full

86 A/Aicda), Rev1 and Ung (central elements for CSR/SHM), and Bcl6, Bach2, or Pax5 (repressors of PRDM1/

87 showed that Rad54 was neither essential for CSR, RCR nor RDR, and it had no significant influence on

88 Significant correlation was found for CSR chemical-shift ratio (r = -0.761) and SII signal int

89 SReport will provide a unified framework for CSR junction studies.

90 DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromos

91 tes DNA strand incisions (a prerequisite for CSR) at these abasic sites, a direct test of the require

92 of sequences from our HTS-based protocol for CSR junctions, thereby facilitating and accelerating the

93 est that 3'RR is not absolutely required for CSR and, thus, is not essential for targeting activation

94 The AID C terminus is required for CSR, but not for S-region DNA double-strand breaks (DSBs

95 Uracil glycosylase 2 (UNG2) is required for CSR, most likely by removing uracils to generate abasic

96 s, and the double-strand breaks required for CSR.

97 tis establishes a conserved nuclear role for CSR-1 and highlights its key role in germline gene regul

98 on-Gurwitz et al. now demonstrate a role for CSR-1 and its slicer activity in downregulating the leve

99 ignificant correlation with age was seen for CSR chemical-shift ratio (r = 0.702, P < .001) but not S

100 m BRCT domain of PTIP that is sufficient for CSR and identified PA1 as its main functional protein pa

101 of C region (CH) loci that are targeted for CSR in a cytokine-dependent fashion in mature B lymphocy

102 , as emphasized by the significantly greater CSR reduction in Rad52(-/-) versus Rad52(+/+) B cells on

103 r SII signal intensity index between groups; CSR chemical-shift ratio values overlapped in a few youn

104 iscuss several aspects of CSR, including how CSR is induced, CSR in B cell progenitors, the roles of

105 ted a profound influence on LDC-mediated IgA CSR.

106 IgD CSR is a rare event, and its regulation is poorly unders

107 IgD CSR occurred via both alternative nonhomologous end-join

108 Microbiota-dependent IgD CSR also was detected in nasal-associated lymphoid tissu

109 signal via Toll-like receptors to elicit IgD CSR.

110 of secreted IgD resulting from increased IgD CSR exclusively within B cells of mucosa-associated lymp

111 Regulation of rare IgD CSR events has been enigmatic.

112 gand-deficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells.

113 Exome sequencing in 2 immunoglobulin CSR-D patients identified variations in the INO80 gene.

114 atients affected by defective immunoglobulin CSR.

115 be associated with defective immunoglobulin CSR.

116 However, many immunoglobulin CSR-Ds are still undefined at the molecular level.

117 as to delineate new causes of immunoglobulin CSR-Ds and thus gain further insights into the process o

118 sess the function of INO80 on immunoglobulin CSR.

119 Impaired CSR can be rescued by ectopic expression of Mbd4 Mbd4 de

120 its regulatory subunits results in impaired CSR and increased usage of microhomology-based end joini

121 knockdown in CH12 cells results in impaired CSR.

122 l as its partners Reptin and Pontin impaired CSR.

123 of healthy subjects, revealing that impaired CSR does not interfere with the peripheral B cell tolera

124 However, impairing CSR-1 has very little effect on the accumulation of its

125 -glycosylase (UNG) deficiency, which impairs CSR but not SHM.

126 G4 recognition and oligomerization of AID in CSR.

127 a direct test of the requirement for APE1 in CSR has been difficult because of the embryonic lethalit

128 hing to IgG3 and IgG2b, as well as delays in CSR kinetics associated with defective proliferation dur

129 Differences in CSR chemical-shift ratio and SII signal intensity index

130 d the roles of certain DNA-repair enzymes in CSR.

131 Our results identify BRIT1 as a factor in CSR and demonstrate that multiple BRCT-domain proteins c

132 of transcription and chromosomal looping in CSR, and the roles of certain DNA-repair enzymes in CSR.

133 e establish a critical role for p110alpha in CSR.

134 ced by DeltaAID are unable to participate in CSR and might interfere with the ability of full-length

135 ability of full-length AID to participate in CSR.

136 r efforts include reviewing and recording in CSR available clinical information on patients, mapping

137 ed Igh breaks and a significant reduction in CSR in ex vivo activated splenic B cells.

138 the CH12F3 cell line to explore its role in CSR.

139 ate immunity, but with no recognised role in CSR.

140 ding p110alpha and p110delta, whose roles in CSR remain unknown or controversial.

141 ormal CSR, Rad52(-/-) B cells show increased CSR, fewer intra-Smu region recombinations, no/minimal m

142 d cultured with IL-4 and anti-CD40 to induce CSR to IgE.

143 Similarly, we induce CSR in all human B cell lines tested with high efficienc

144 spects of CSR, including how CSR is induced, CSR in B cell progenitors, the roles of transcription an

145 X-box binding protein 1, thereby inhibiting CSR, SHM, and plasma cell differentiation without alteri

146 ontaining the catalytic SET domain, inhibits CSR without affecting either IgH germline transcription

147 at) 6, and demonstrate a failure to initiate CSR to IgG1 with low expression of gamma1 germ-line tran

148 n-induced cytidine deaminase (AID) initiates CSR by promoting deamination lesions within Smu and a do

149 ative frequency of deletional to inversional CSR junctions has not been measured.

150 se pro-B-cell lines, dispensable for joining CSR-associated DSBs in a cycling mouse B-cell line, and

151 al divergent eRNA-expressing element (lncRNA-CSR) engaged in long-range DNA interactions and regulati

152 CRISPR-Cas9-mediated ablation of lncRNA-CSR transcription decreases its chromosomal looping-medi

153 Mean CSR chemical-shift ratio and SII signal intensity index

154 targets this enzyme to S regions to mediate CSR.

155 Moreover, CSR in APE1-null CH12F3 cells is drastically reduced, pr

156 ad52(+/+) counterparts, which display normal CSR, Rad52(-/-) B cells show increased CSR, fewer intra-

157 during SHM and that despite globally normal CSR function in splenic B cells, Fanca is required durin

158 I3K isoforms is essential to maintain normal CSR.

159 translocation and mutation frequency but not CSR or Ig switch region mutation.

160 We conclude that SHM, but not CSR, regulates peripheral B cell tolerance through the p

161 Discrimination abilities of CSR chemical-shift ratio and SII signal intensity index

162 mokines CCL22 and CCL17 in the activation of CSR.

163 ion about the CSR mechanism, and analysis of CSR junctions is useful in basic and clinical research s

164 are program dedicated to support analysis of CSR recombination junctions sequenced with a HTS-based p

165 We discuss several aspects of CSR, including how CSR is induced, CSR in B cell progeni

166 We demonstrate that the association of CSR-1 with chromatin is preserved, and show that depleti

167 Lower doses of CSR and smaller boost volumes seem to mitigate intellect

168 BRCT-domain protein BRIT1 as an effector of CSR.

169 mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses.

170 ining is a programmed mechanistic feature of CSR as it is for V(D)J recombination and, if so, how thi

171 Amount and structural features of CSR junctions reveal valuable information about the CSR

172 In both groves, the hypothesis of CSR was rejected for all tests performed including quadr

173 ate the mediator complex in the mechanism of CSR and are consistent with a model in which mediator fa

174 cate the cohesin complex in the mechanism of CSR by showing that cohesin is dynamically recruited to

175 However, the proportion of CSR translocations is not consistent between cytogenetic

176 males also harbor an extensive repertoire of CSR-1 small RNAs targeting oogenesis-specific mRNAs.

177 t genes between species, we defined a set of CSR-1 target genes with conserved germline expression, e

178 ated tool able to analyze large data sets of CSR junction sequences produced by high-throughput seque

179 rt was assessed using simulated data sets of CSR junctions and then used for analysis of Smu-Salpha a

180 T1-deleted B cells increases the severity of CSR defect over what is observed upon loss of either pro

181 tivity-dependent dominant-negative effect on CSR.

182 e, we demonstrate a direct effect of PTEN on CSR signaling by acute deletion of Pten specifically in

183 d SHM and CSR pipeline to analyze SHM and/or CSR in BCR rearrangements.

184 tosis with XY male-to-female sex reversal or CSR.

185 hyperplasia from tumors, although overlapped CSR chemical-shift ratio values can occur in early adult

186 78H) (Lig4(R/R)) mice exhibit only a partial CSR block, producing near normal IgG1 and IgE but substa

187 for mutagenic NHEJ but not for physiological CSR.

188 ecifically eliminating E5 not only precludes CSR but also, causes an atypical, enzymatic activity-dep

189 Productive CSR must occur in a deletional orientation by joining th

190 53BP1 promotes CSR in part by mediating synapsis of distal DNA ends, an

191 g evidence that 3'RR has a role in promoting CSR that is unique from enhancing S region transcription

192 es, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to li

193 s overlaid on a completely spatially random (CSR) background, before every point is scrambled by its

194 e hypothesis of complete spatial randomness (CSR) of CBS infected trees within the groves.

195 Class-switch DNA recombination (CSR) and somatic hypermutation (SHM), which require acti

196 Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (

197 Class-switch recombination (CSR) alters the Ig isotype to diversify antibody effecto

198 o immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma ce

199 during antibody class switch recombination (CSR) and DSBs generated by ionizing radiation.

200 for Flt3 in IgG1 class-switch recombination (CSR) and production.

201 e find that both class switch recombination (CSR) and R-loop formation decrease significantly when th

202 (AID) initiates class switch recombination (CSR) and somatic hypermutation (SHM) by deaminating cyto

203 ) initiates both class switch recombination (CSR) and somatic hypermutation (SHM) in antibody diversi

204 AID mediates class-switch recombination (CSR) and somatic hypermutation (SHM) in B cells, but the

205 is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes.

206 enzyme-mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin g

207 tion mechanisms, class switch recombination (CSR) and somatic hypermutation (SHM), to re-engineer the

208 dine to initiate class-switch recombination (CSR) and somatic hypermutation.

209 d immunoglobulin class switch recombination (CSR) are key processes in adaptive immune responses that

210 abnormalities in class switch recombination (CSR) associated with the human homozygous Lig4 R278H mut

211 DCs induced IgA class-switch recombination (CSR) by activating B cells through T cell-dependent or -

212 tation (SHM) and class switch recombination (CSR) by deaminating cytidines to uridines at V region (V

213 Class switch recombination (CSR) diversifies antibodies for productive immune respon

214 tation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (Ig

215 unoglobulin (Ig) class switch recombination (CSR) enable B cells to produce high-affinity antibodies

216 mature B cells, class switch recombination (CSR) generates different antibody classes by replacing C

217 Class switch recombination (CSR) generates isotype-switched Abs with distinct effect

218 ID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the Ig

219 lymphocytes and class switch recombination (CSR) in antigen-stimulated B cells.

220 riggers antibody class switch recombination (CSR) in B cells by initiating DNA double strand breaks t

221 Antibody class switch recombination (CSR) in B lymphocytes joins two DNA double-strand breaks

222 tation (SHM) and class-switch recombination (CSR) increase the affinity and diversify the effector fu

223 lymphocytes, Ig class switch recombination (CSR) is induced by activation-induced cytidine deaminase

224 unoglobulin (Ig) class switch recombination (CSR) is initiated by activation-induced cytidine deamina

225 In B cells, Ig class switch recombination (CSR) is initiated by activation-induced cytidine deamina

226 unoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitme

227 Class switch recombination (CSR) is instigated by activation-induced cytidine deamin

228 IgH class switch recombination (CSR) occurs through the deliberate introduction of activ

229 tation (SHM) and class switch recombination (CSR) of antibody genes.

230 domas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass.

231 tation (SHM) and class switch recombination (CSR) pipeline.

232 Class switch recombination (CSR) plays an important role in adaptive immune response

233 tation (SHM) and class-switch recombination (CSR) processes.

234 ulin heavy chain class switch recombination (CSR) requires targeted formation of DNA double-strand br

235 low frequency of class switch recombination (CSR) to IgE ex vivo.

236 Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to at

237 age for antibody class switch recombination (CSR) via transcription-dependent cytidine deamination of

238 IgH expression, class-switch recombination (CSR), and somatic hypermutation.

239 g immunoglobulin class switch recombination (CSR), are repaired by non-homologous end joining (NHEJ).

240 is essential for class switch recombination (CSR), but no molecular function of the transcripts has b

241 rmutation (SHM), class-switch recombination (CSR), or both.

242 reaks (DSBs) for class-switch recombination (CSR).

243 regulation of Ig class switch recombination (CSR).

244 f immunoglobulin class-switch recombination (CSR).

245 tation (SHM) and class switch recombination (CSR).

246 D)-dependent IgH class switch recombination (CSR).

247 during IgH (Igh) class-switch recombination (CSR).

248 o not undergo Ig class switch recombination (CSR).

249 l center through class switch recombination (CSR).

250 eavy chain (Igh) class switch recombination (CSR).

251 pe class switch (class switch recombination [CSR]).

252 eficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introd

253 core component of the NHEJ pathway, reduces CSR efficiency in a mouse B-cell line capable of robust

254 ive patients with cancer-suspicious regions (CSRs) on multiparametric MR images obtained at 3 T.

255 uster-situated (transcriptional) regulators (CSRs) of the biosynthetic genes.

256 formational/stereoselectivity relationships (CSR) between catalysts and substrates provide a framewor

257 ree modes: complementary strand replication (CSR), rolling circle replication (RCR) and recombination

258 and proportion of Cheyne-Stokes Respiration [CSR]).

259 of E. cyaneus) and cellular stress response (CSR) capacity, potentially causing species-related diffe

260 (lacking the large spacer regions) restores CSR to a level equivalent to or even higher than in wild

261 characterized by chronic sleep restriction (CSR) rather than by episodic TSD, the practical utility

262 of subjects with chronic sleep restriction (CSR).

263 onic ( approximately 5 d) sleep restriction (CSR).

264 the predominant mechanism catalyzing robust CSR.

265 mouse B cell line (CH12F3) capable of robust CSR in vitro.

266 Such frequent joining of widely separated CSR DSBs could be promoted by IgH-specific or B-cell-spe

267 l line capable of robust cytokine-stimulated CSR in cell culture.

268 e for p110alpha and p110delta in suppressing CSR.

269 2AX are required for efficient class switch (CSR) and V(D)J recombination in part because they protec

270 munoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT do

271 better with SII signal intensity index than CSR chemical-shift ratio .

272 sing confocal microscopy, we then found that CSR but not SD mice show morphological signs of microgli

273 Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm

274 We then tested the hypothesis that CSR compromises microvascular function.

275 Here, we report that CSR levels are not further reduced by deletion of either

276 We show that CSR is programmed to occur in a productive deletional or

277 We suggest that CSR exploits a general propensity of intrachromosomal DS

278 ctions reveal valuable information about the CSR mechanism, and analysis of CSR junctions is useful i

279 otypic composition of tonsil B cells and the CSR to IgE ex vivo.

280 Caenorhabditis briggsae to characterize the CSR-1 pathway, its targets and their evolution.

281 l as the entire study are available from the CSR website.

282 our hypersensitive sites contain most of the CSR-promoting functions of 3'RR.

283 Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin l

284 Here, we show that the CSR-1 Argonaute functions with ALG-3/4 to positively reg

285 the binding of biosynthetic products to the CSR has been shown to provide negative feedback.

286 egion of the gene encoding SgcR1, one of the CSRs of lidamycin production.

287 late AID expression are of much relevance to CSR and genomic integrity; however, effectors of such re

288 ad52 and translesion DNA polymerase theta to CSR.

289 data from three prior studies involving TSD, CSR, and sleep extension.

290 of IgH in ATM-deficient, but not wild-type, CSR-activated B cells.

291 B cells that did not express AID or undergo CSR.

292 ontrols the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently prom

293 heterozygous for this mutant fail to undergo CSR.

294 Finally, we show that in B cells undergoing CSR, the dynamic long-range contacts between the IgH enh

295 alterations in S region DSBs when undergoing CSR.

296 ost exclusively in those that have undergone CSR.

297 cells resulted in decreased rates of ex vivo CSR.

298 mechanism and provide an explanation of why CSR is so reliant on the 53BP1 DSB-response factor.

299 th V(D)J recombination, DSBs associated with CSR can be resolved in NHEJ-deficient cells (albeit at a

300 suppress genomic instability associated with CSR.

301 onal regulation, and by (2) functioning with CSR-1 to limit the domain of sperm-specific expression a