ライフサイエンスコーパス: R-loop

1 ease 1 (FEN1) cleavage of TNRs engaged in an R-loop.

2 taneous removal of the dCas9 protein and the R-loop.

3 d as ssDNA and forming a structure called an R-loop.

4 ermanent genetic tags for the position of an R-loop.

5 circuitry that safeguards the genome against R loops.

6 ranscriptional RNA-DNA helicase that unwinds R loops.

7 prostate cancer PC3 cells leads to increased R-loops.

8 ymatic activities and their influence on TNR R-loops.

9 ttling, as well as colocalization of Gle1 at R-loops.

10 A superhelicity, plays a key role in driving R-loops.

11 bed DNA replication through the avoidance of R-loops.

12 vated topoisomerase I, a known restrainer of R-loops.

13 kely occurs because of proteins bound to the R-loops.

14 uding RNaseH that degrades the RNA moiety in R-loops.

15 SA2 binding sites overlap significantly with R-loops.

16 RNA abasic sites were found to be coupled to R-loops.

17 including ssRNA, dsRNA, RNA:DNA hybrids, and R-loops.

18 Finally, we demonstrated that TERRA R-loops accumulate at telomeres in FANCM deficient ALT c

19 We demonstrate that m(6)A-containing R-loops accumulate during G(2)/M and are depleted at G(0

20 In response to aberrant R loop accumulation, the ataxia telangiectasia and Rad3-

21 with ZPR1 elevates senataxin levels, reduces R-loop accumulation and rescues DNA damage in SMA mice,

22 Ectopic R-loop accumulation causes DNA replication stress and ge

23 nts that are thought to increase or decrease R-loop accumulation enhance or suppress, respectively, t

24 ps formed from different sources and prevent R-loop accumulation genome-wide at actively transcribed

25 ROS-induced DNA damage at telomeres triggers R-loop accumulation in a TERRA- and TRF2-dependent manne

26 Accordingly, PHF2 depletion induces R-loop accumulation that leads to extensive DNA damage a

27 find that mitotic defects, and in some cases R-loop accumulation, are causes of genome instability.

28 We show that UAP56 depletion causes R-loop accumulation, R-loop-mediated genome instability,

29 Cells have different ways to prevent R-loop accumulation.

30 Biochemically, R-loops act as intrinsic Pol II promoters to induce de n

31 Consequently, we predict that R-loops act to facilitate the synthesis of many gene pro

32 We conclude that whereas R-loops alone can act as transient replication blocks, m

33 and show that its overexpression suppresses R loops and genome instability induced by depleting five

34 be able to stabilize both G-quadruplexes and R loops and showed a potent cell killing activity associ

35 Finally, we show that TbRH2A loss causes R-loop and DNA damage accumulation in telomeric RNA Pol

36 ast cancer cells increases intensity of this R-loop and reduces transcription of its neighboring gene

37 le-strand breaks, we show that it suppresses R-loops and associated DNA damage at transcription-repli

38 hat BRD4 inhibition leads to accumulation of R-loops and DNA damage at a subset of known BDR4, JMJD6,

39 mammary epithelium was performed to quantify R-loops and DNA damage in vivo.

40 SMN cause accumulation of co-transcriptional R-loops and DNA damage leading to genomic instability an

41 reventing accumulation of co-transcriptional R-loops and DNA damage to avert genomic instability and

42 R-loops and DNA damage were also detected in mammary epi

43 In vitro, both PRC1 and PRC2 can recognize R-loops and open DNA bubbles.

44 ibonuclease 2 (XRN2) degrades RNA to resolve R-loops and promotes transcription termination.

45 ment helicase for replication bypass of both R-loops and protein blocks.

46 echanism is mediated by an interplay between R-loops and RING1B recruitment.

47 intimate spatiotemporal relationship between R-loops and RNA polymerase II pausing/pause release, as

48 Both antisense only (ASO)-R-loops and sense/antisense (S/AS)-R-loops sharply peake

49 elationship between transcription stress and R-loops and suggest that different classes of R-loops ma

50 eads to the accumulation of RNA:DNA hybrids (R-loops) and collisions with the replication machinery c

51 ation of co-transcriptional RNA-DNA hybrids (R-loops) and DNA damage leading to genomic instability i

52 polymerase II (RNAPII) transcription stress, R-loops, and genome instability have been established, t

53 eq permits the recovery of the RNA moiety of R-loops, and these RNA strands are subjected to strand-s

54 exes [r(GAA):d(TTC) and d(GAA):r(UUC)] in an R-loop; and three hybrid triplexes that could form durin

55 In the collapsed R-loops, antiparallel d(TTC+).d(GAA):r(UUC) is unstable,

56 G quadruplexes (G4s) and R loops are noncanonical DNA structures that can regulat

57 R-loops are a prevalent class of non-B DNA structures th

58 R-loops are abundant three-stranded nucleic-acid structu

59 DNA triplexes and R-loops are believed to arrest transcription, which resu

60 R-loops are common across many domains of life and cause

61 R-loops are common in the genomes of pro- and eukaryotes

62 R-loops are dynamic, co-transcriptional nucleic acid str

63 R-loops are implicated in various basic nuclear processe

64 Recent evidence suggests that R-loops are involved in a number of human diseases, incl

65 R-loops are nucleic acid structures formed by an RNA:DNA

66 In addition, stabilized R-loops are observed at the 70 bp repeats and immediatel

67 r accurate normalization in conditions where R-loops are perturbed and for quantitative measurements

68 We recently showed that R-loops are preferentially accumulated in breast luminal

69 R-loops are prevalent three-stranded non-B DNA structure

70 R-loops are RNA-DNA hybrid sequences that are emerging p

71 R-loops are three-stranded nucleic acid structures that

72 R loops arise from hybridization of RNA transcripts with

73 R loops arising during transcription induce genomic inst

74 iew, we summarize recent results implicating R-loops as important regulators of cellular processes su

75 They also reveal R-loops as powerful and reversible topology sinks that c

76 of transcription-associated RNA-DNA hybrids (R-loops) as inhibition of BRD2 or BRD4 increased R-loop

77 The R-loop assay was used to screen a series of rationally d

78 ic instability, but how cells respond to the R loop-associated genomic stress is still poorly underst

79 We show that R-loop-associated chromosomal instability can be induced

80 ly because dCas9 induces the formation of an R-loop at its target site.

81 s R-loops to investigate the consequences of R-loops at CEN chromatin and chromosome segregation.

82 We determined that accumulation of R-loops at CEN chromatin contributes to defects in kinet

83 iant, Cse4, and prevents the accumulation of R-loops at CEN chromatin for chromosomal stability.

84 on (DRIP) analysis showed an accumulation of R-loops at CEN chromatin that was reduced by overexpress

85 echanistic insights into how accumulation of R-loops at CEN contributes to defects in kinetochore int

86 e mediated by formation of ERalpha-dependent R-loops at concentrations 10-fold lower than those requi

87 While MRN has been shown to promote R-loops at DNA double-strand breaks, we show that it sup

88 ing triplex nucleic acid structures known as R-loops at intergenic spacers flanking nucleolar rRNA ge

89 R-loops at the 5' and 3' ends of the RA or E(2)-target g

90 tive ES transcription favors accumulation of R-loops at the telomere and 70 bp repeats, providing an

91 bypass an inactive (i.e., dead) Cas9 (dCas9) R-loop barrier.

92 NA sequences by inducing the formation of an R-loop between the guide RNA and its genomic target.

93 updated view of much-needed future goals in R-loop biology.

94 basis for the emerging field of quantitative R-loop biology.

95 ATR protects the genome from R loops by suppressing transcription-replication collisi

96 Finally, counteracting R-loops by INO80 promotes proliferation and averts DNA d

97 One such mechanism is hydrolysis of R-loops by ribonuclease HI (RNase HI).

98 Second, R-loops, by absorbing negative superhelicity, partially

99 e also highlight recent work suggesting that R-loops can be problematic to cells as blocks to efficie

100 replication machinery and co-transcriptional R-loops can impede DNA synthesis and are a major source

101 However, it remains unknown how BER in R-loops can mediate TNR instability.

102 At an elevated level, telomere R-loops cause more telomeric and subtelomeric double-str

103 In vitro transcription assays confirmed that R-loops cause plasmid relaxation and that negative super

104 Cells encode several RNA polymerase and R-loop clearance mechanisms to limit replisome exposure

105 R-loops co-localize with and promote recruitment of INO8

106 n engages DNA exposed within the CRISPR-Cas9 R-loop complex.

107 etic ablation confirms the relevance of this R-loop-containing region to enhancer-promoter interactio

108 Several studies have uncovered that R-loops contribute to fundamental biological processes i

109 The persistent presence of R-loops contributes to defects in DNA replication and re

110 asic site on the nontemplate strand of a TNR R-loop, creating a double-flap intermediate containing a

111 In addition, integrative analyses of R-loop data with existing RNA-seq, chromatin immunopreci

112 Based on the largest single-molecule R-loop dataset to date, we show that individual R-loops

113 NF-kappaB-driven innate immune responses to R-loop-dependent replication stress and DNA damage.

114 Our results reveal that R-loops differ by their architectures and that the organ

115 I assess the discovery of the mitochondrial R-loop, discuss why it remained unrecognized for almost

116 Accurately mapping R-loop distribution in various cell lines and under vari

117 SMRF-seq further established that R-loop distribution patterns are not simply driven by in

118 rovide a complementary and congruent view of R-loop distribution, consolidating our understanding of

119 replication by suppressing the formation of R-loops (DNA/RNA-hybrids).

120 BRCA1 is implicated in resolving R-loops, DNA-RNA hybrid structures associated with genom

121 ctural alterations on RNP complex formation, R-loop dynamics, and endonuclease activity.

122 (7)), interacts with R-loop-enriched loci in dividing cells.

123 We conducted genome-wide identification of R-loops followed by integrative analyses of R-loops with

124 Single-molecule R-loop footprinting coupled with PacBio sequencing (SMRF

125 e microscopy approaches with single molecule R-loop footprinting to demonstrate that R-loops formed a

126 cBio sequencing allows the identification of R-loop 'footprints' at near nucleotide resolution in a s

127 an DNA polymerases can utilize RPA-generated R-loops for initiation of DNA synthesis, mimicking the p

128 Here, we show that R-loops form at a subset of Polycomb target genes, and w

129 Here we show that R-loops form at many PREs in Drosophila embryos, and cor

130 i-DNA:RNA hybrid S9.6 antibody revealed that R-loops form dynamically over conserved genic hotspots.

131 oop dataset to date, we show that individual R-loops form nonrandomly, defining discrete sets of over

132 fite-based R-loop mapping and confirmed that R-loops form over genic hotspots, including gene bodies

133 R-loops form universally in the genomes of organisms ran

134 f only two or three nucleotides could reduce R-loop formation and cleavage activity of the RuvC domai

135 unwinding of the double helix, we find that R-loop formation and collapse proceed via a transient di

136 Here we investigate the dynamics of Cas9 R-loop formation and collapse using rotor bead tracking

137 percoiling modulates the energy landscape of R-loop formation and dictates access to states competent

138 R-loop formation and DNA cleavage activity were also ess

139 H1 can be expressed to study the dynamics of R-loop formation and resolution, as well as its impact o

140 DNA sequence and DNA topology in controlling R-loop formation and stability.

141 of PrimPol leads to significantly increased R-loop formation around this repeat during S phase.

142 Our results identify R-loop formation as a feature of Drosophila PREs that ca

143 t repriming limits the extent of unscheduled R-loop formation at these sequences, mitigating their im

144 Here, we show in vivo how R-loop formation drives a short purine-rich repeat, (GAA

145 BP-3 and PP exposure caused R-loop formation in a normal human breast epithelial cel

146 servation by showing that PrimPol suppresses R-loop formation in genes harbouring secondary structure

147 statistical mechanical equilibrium model of R-loop formation in superhelical DNA.

148 Experimental evidence suggests that R-loop formation is affected by DNA sequence and topolog

149 A dynamic and mechanical description of R-loop formation is needed to understand the biophysics

150 However, the mechanism of R-loop formation remains unknown.

151 /pause release, as well as linking augmented R-loop formation to DNA damage response induced by drive

152 idating the computationally-identified RLFS, R-loop formation was experimentally confirmed in the TR

153 , by forming a complex with RNA, can promote R-loop formation with homologous dsDNA.

154 ops) as inhibition of BRD2 or BRD4 increased R-loop formation, which generated DSBs.

155 gation arises from the transcription-induced R-loop formation, which in turn generates G4 structure i

156 d, non-canonical small subunits to stabilize R-loop formation.

157 r protospacer-adjacent motif recognition and R-loop formation.

158 as a PRC2 activity that could contribute to R-loop formation.

159 ongation, splicing, alternative splicing and R-loop formation.

160 e that relaxes DNA supercoiling and prevents R-loop formation.

161 erties of human RPA and its possible role in R-loop formation.

162 y a mechanism involving successive rounds of R-loop formation.

163 r understanding of the principles underlying R-loop formation.

164 AP56 helicase activity is required to remove R loops formed from different sources and prevent R-loop

165 cule R-loop footprinting to demonstrate that R-loops formed at the model Airn locus in vitro adopt a

166 te prevalence, distribution, and location of R-loop forming sequences (RLFS) across more than 6000 vi

167 ion of RNA-DNA hybrids, the key component of R-loops, from RNA and dsDNA.

168 elationships and intricate connections among R-loops, gene expression, and epigenetic signatures.

169 By leveraging the orthogonal R-loops generated by SaCas9 nickase to mimic actively tr

170 trategy, named R-ChIP, for robust capture of R-loops genome-wide.

171 R-loops have both positive and negative impacts on chrom

172 R-loops have not been detected at centromeric (CEN) chro

173 aches to map RNA-DNA hybrids, a component of R-loops, have so far not allowed quantitative comparison

174 ding strand, whereas lagging-strand template R-loops (head-on) had little impact on replication fork

175 r in which genotoxic DNA:RNA hybrids, called R-loops, impair DNA replication.

176 suggest that m(6)A regulates accumulation of R-loops, implying a role for this modification in safegu

177 cell making it potentially the most abundant R-loop in nature.

178 iates DNA cutting by forming a 20-nucleotide R-loop in which the guide RNA displaces one strand of a

179 This model reveals R-loops in a new light as powerful and reversible topolo

180 ecent studies have pointed toward a role for R-loops in causing TNR expansion and deletion, and it ha

181 of INO80 to a LacO locus enabled turnover of R-loops in cis.

182 lights recent studies indicating the role of R-loops in DNA double-strand break repair with an update

183 To identify toxic R-loops in the human genome, here, we map RNA:DNA hybrid

184 nd briefly discusses methods for identifying R-loops in vivo It also highlights recent studies indica

185 (BER) can result in CAG repeat deletion from R-loops in yeast.

186 t loci prone to form G-quadruplex-associated R-loops, in a process that is dependent on its helicase

187 his model, the energy involved in forming an R-loop includes four terms-junctional and base-pairing e

188 activation of ATR by replication inhibitors, R loop-induced ATR activation requires the MUS81 endonuc

189 t that ATR is a key sensor and suppressor of R loop-induced genomic instability, uncovering a signali

190 3-related (ATR)-Chk1 pathway is activated by R loop-induced reversed replication forks.

191 and DNA breaks (SSBs and DSBs) contribute to R-loop induction, promoting the localization of CSB and

192 In viruses, R-loop investigation is limited and functional importanc

193 hole genome BRD4 and gammaH2AX ChIP-Seq with R-loop IP qPCR reveals that BRD4 inhibition leads to acc

194 An R-loop is a three-stranded nucleic acid structure that c

195 This mitochondrial R-loop is present on thousands of copies of mitochondria

196 s, which could explain that only a subset of R-loops is associated with replication-dependent DNA bre

197 terestingly, DNA flanking the RNA-5' side of R-loops is not intrinsically unstable.

198 The rising interest in R-loops is placing new emphasis on understanding the fun

199 Unrepaired R loops lead to transcription-replication collisions, ca

200 The G4 stabilized R-loop leads to increased transcription by a mechanism i

201 abilize G-quadruplex structures and increase R loop levels in human cancer cells.

202 However, modulating R-loop levels by controlling RNase HI expression does no

203 The molecular characterization of R-loop levels in patient-derived cells provides insight

204 regulation of the telomere and 70 bp repeat R-loop levels is important for the balance between antig

205 ds stabilize G4s and simultaneously increase R-loop levels within minutes in human cancer cells.

206 equently, YTHDF2 knockout leads to increased R-loop levels, cell growth retardation and accumulation

207 the Glu385Lys variant leads to a decrease in R loops, likely from a gain of function.

208 The majority of R-loop-localized SA1 and SA2 are also sites where other

209 te the impact of a BRCA1 mutation-associated R-loop located in a putative transcriptional enhancer up

210 ement between S9.6-based and bisulfite-based R-loop mapping and confirmed that R-loops form over geni

211 teration of the method that permits accurate R-loop mapping genome wide.

212 Distinct from R-loop-mapping methods based on the monoclonal antibody

213 -loops and suggest that different classes of R-loops may exist, potentially with distinct consequence

214 hese outcomes, cells possess a range of anti-R-loop mechanisms, including RNaseH that degrades the RN

215 To comprehensively identify anti-R-loop mechanisms, we performed a genome-wide trigenic i

216 is review focuses on the molecular basis for R-loop-mediated gene regulation and genomic instability

217 UAP56 depletion causes R-loop accumulation, R-loop-mediated genome instability, and replication fork

218 Perturbations in R-loop metabolism have been linked to genomic instabilit

219 Our findings suggest that BRCA1-dependent R-loop mitigation contributes to luminal cell-specific t

220 Factoring in recent developments in R-loop modeling and single-molecule profiling, we propos

221 noncoding RNAs, and establish locus-targeted R-loop modulation.

222 R-loops most often map to intronic regions and their ind

223 Stable removal of PRC2 derepresses R-loop-negative genes, as expected, but does not affect

224 s experiments revealed that the formation of R-loop objects at Airn is dictated by the extruded non-t

225 Interestingly, we show that these R-loop objects impose specific physical constraints on t

226 y distinct shapes and volumes, which we call R-loop objects.

227 R-loops occur frequently in genomes and have significant

228 n the other hand, replisomes easily bypassed R-loops on either template strand.

229 Replication encounters with R-loops on the leading-strand template (co-directional)

230 of both DNA and histone marks can influence R-loop peak levels on a genome-wide scale.

231 between gene expression levels and profiled R-loop peak levels was dependent on the positions of R-l

232 At R-loop-positive genes, R-loop removal leads to decreased

233 ecruitment, or transcriptional repression of R-loop-positive genes.

234 xtruded non-template strand, suggesting that R-loops possess intrinsic sequence-driven properties.

235 that significantly expands the repertoire of R-loops' potential biological roles under both normal an

236 tive genes, as expected, but does not affect R-loops, PRC1 recruitment, or transcriptional repression

237 Our results indicate that TNR R-loops preferentially lead to repeat deletion during BE

238 the TTS of highly expressed genes containing R-loops prevents head-on conflicts between replication a

239 Thus, ROS-induced telomeric R-loops promote repair of telomeric DSBs through CSB-RAD

240 Thus, R-loops promote the creation of replication blocks at su

241 suggests that INO80-dependent resolution of R-loops promotes DNA replication in the presence of tran

242 we show that cells harboring high levels of R loops rely on the ATR kinase for survival.

243 At R-loop-positive genes, R-loop removal leads to decreased PRC1 and PRC2 recruitm

244 investigated the function of UAP56/DDX39B in R-loop removal.

245 iption is mitigated by ectopic expression of R-loop-removing RNase H1.

246 Nonscheduled R loops represent a major source of DNA damage and repli

247 axin loss, Ewing sarcoma or locus-associated R-loop repression through an experimental system involvi

248 Perturbations of transcription or R-loop resolution are expected to change their genomic d

249 tly, but also promote DSB repair by inducing R-loops, revealing an unexpected interplay between disti

250 Persistent R-loops (RNA-DNA hybrids with a displaced single-strande

251 nly (ASO)-R-loops and sense/antisense (S/AS)-R-loops sharply peaked around transcription start sites

252 Genome-wide mapping of R loops showed that the studied G4 ligands likely cause

253 An increase in nuclear R-loop signal intensity was also observed with diminishe

254 We directly compared the SA1/SA2 binding and R-loops sites extracted from Chromatin Immunoprecipitati

255 equence and DNA superhelicity in controlling R-loop stability.

256 een DNA sequence and DNA topology in driving R-loop structure formation.

257 This asymmetry in R-loop structure may explain the uniformity of guide RNA

258 ated guide RNA to one DNA strand, forming an R-loop structure.

259 R-loop structures are a prevalent class of alternative n

260 iction digestion with a cocktail of enzymes, R-loop structures are immunoprecipitated with the anti-R

261 Three-stranded R-loop structures have been associated with genomic inst

262 mmunoprecipitation-based methods for mapping R-loop structures: basic DRIP-seq (DNA-RNA immunoprecipi

263 ytic function of MRE11 that is important for R-loop suppression by the Fanconi Anemia pathway.

264 by which these factors interact to determine R-loop susceptibility is unclear.

265 Interestingly, dCas9 R-loops targeted to either strand are bypassed with simi

266 ed RNP formation but produced a stable ~9 bp R-loop that could not activate DNA cleavage.

267 RNase HI/SSB interaction in helping to clear R-loops that block DNA replication.

268 iers can include transcription complexes and R-loops that form when RNA hybridizes with complementary

269 sence of co-transcriptional RNA/DNA hybrids (R-loops) that form in infected cells during S-phase as a

270 R-loops, the byproduct of DNA-RNA hybridization and the

271 repair in vitro and associates in vivo with R-loops, the three-stranded structures consisting of an

272 nts that reveals novel functional aspects of R-loops, their interrelations with epigenetic methylatio

273 However, it is unclear whether the R-loops themselves are sufficient to cause this instabil

274 R-loops, three-stranded nucleic acid structures comprisi

275 n bypass synthesis and the resolution of TNR R-loops through BER.

276 RAD52 is recruited to telomeric R-loops through its interactions with both CSB and DNA:R

277 ied G4 ligands likely cause the spreading of R loops to adjacent regions containing G4 structures, pr

278 that negative superhelicity is required for R-loops to form, even in a favorable region.

279 we used an hpr1Delta strain that accumulates R-loops to investigate the consequences of R-loops at CE

280 delling INO80 complex promotes resolution of R-loops to prevent replication-associated DNA damage in

281 How cancer cells deal with R-loops to proliferate is poorly understood.

282 collisions with transcription complexes and R-loops using a reconstituted bacterial DNA replication

283 eveloped an orthogonal approach that queries R-loops via the presence of long stretches of single-str

284 Formation of R-loops was determined with DNA: RNA hybrid-specific S9.

285 In contrast, sense only (SO)-R-loops were generally spread over the coding regions, a

286 rand bonds with the hybrid duplex (collapsed R-loops, where the two DNA strands remain antiparallel).

287 three-stranded structure with DNA, called an R-loop, which has been linked to fundamental biological

288 stability in DNA flanking the RNA-3' side of R-loops, which Cas12a can exploit to expose second-stran

289 te strand is a fundamental characteristic of R-loops, which could explain that only a subset of R-loo

290 omote the invasion of the DNA by RNA to form R-loops, which have been shown to block DNA replication

291 (mut) expression also dramatically increases R-loops, which may form at the anterior end of backtrack

292 n the non-target strand of the dCas9-induced R-loop, while others are associated with homopolymer ins

293 Not only are R-loops widely associated with DNA damage and repair, bu

294 A regulation of AS of linear RNAs by forming R-loop with the genomic locus.

295 R-loops followed by integrative analyses of R-loops with relation to gene expression and epigenetic

296 Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be

297 t the G4-sRNA forms a stable RNA:DNA hybrid (R-loop) with its template strand.

298 ng RNA (TERRA), which forms RNA:DNA hybrids (R-loops) with the telomeric DNA.

299 eak levels was dependent on the positions of R-loops within gene structures (hereafter named "genic p

300 olecular clusters that pileup through larger R-loop zones.