ライフサイエンスコーパス: DSB

1 DSB accumulation is increased by suppression of the spin

2 DSB repair occurs as replicated sister chromatids are co

3 DSB repair pathway choice is largely dictated at the ste

4 DSBs are especially dangerous in mitosis when cells go t

5 DSBs proximal to telomeres rarely form COs, likely becau

6 DSBs that disrupt a topological border permit extension

7 esented by the local accumulation of 53BP1), DSB density, and the local chromatin compaction.

8 repair pathway choice, 53BP1 functions as a DSB escort that guards against illegitimate and potentia

9 We have developed a DSB repair assay system, designated CDDR (CRISPR-Cas9-ba

10 present structures of human Polmu engaging a DSB substrate.

11 with Rad55, in suppressing dnTA at or near a DSB.

12 n dissociation, leading in turn to loss of a DSB competent state.

13 mechanism and how the precise location of a DSB may influence genome integrity.

14 Here, we show that chromosomal contacts of a DSB site are the primary determinants for gammaH2Ax land

15 r the juxtaposition of the two DNA ends of a DSB, because all subsequent steps rely on it.

16 the nucleolytic processing (resection) of a DSB, controlling the formation of the 3' single-stranded

17 somes, thereby controlling the duration of a DSB-competent state.

18 cal but not global movement in response to a DSB.

19 proach to enable the measurement of absolute DSB frequencies per cell and their precise genomic coord

20 ic DSBs are generated by Spo11 and accessory DSB proteins, including Rec114 and Mer2, which assemble

21 e demonstrate fosters efficient and accurate DSB repair by controlling Ku and LIG4/XRCC4 activities.

22 reaction using distyrylbenzene-bis-aldehyde (DSB-3), whose reaction with PE produces a fluorescence s

23 Inhibition of autophagy increased levels and DSB recruitment of USP14.

24 redeployment of the chromosome movement and DSB machinery, triggering whole-nucleus reorganisation.

25 e some of the first details of resection and DSB repair intermediates in mouse meiosis using a method

26 , which would be susceptible to both A3B and DSBs.

27 ngle- and double-strand DNA breaks (SSBs and DSBs) contribute to R-loop induction, promoting the loca

28 t ZCWPW1 recognition of PRDM9-bound sites at DSB hotspots is critical for synapsis, and hence fertili

29 h affects the accumulation of BRCA1/BARD1 at DSBs.

30 ol delta promotes Alt-NHEJ in human cells at DSBs, including translocations.

31 IHR at DSBs occurs predominantly via reciprocal end joining.

32 te 53BP1 stability and 53BP1 localization at DSBs.

33 RAD51, resulting in BRCA1/BARD1 retention at DSBs.

34 ncy of IHR is 10-fold lower at nicks than at DSBs, but cnLOH is evident in a greater fraction of reco

35 genomic Cas9/single-guide RNA-generated bait DSBs.

36 dings identify temporal coordination between DSB strand exchange and homolog pairing as a critical de

37 tool, we tested on a 2018 Data Science Bowl (DSB) competition dataset, three users obtained DSB score

38 l mutations at a single double-strand break (DSB) and more frequent translocations between two DSBs.

39 Shot loss leads to double-strand break (DSB) DNA damage, and the apoptotic response is exacerbat

40 nism of any type of DNA double-strand break (DSB) during most of the cell cycle and is essential for

41 egatively regulates DNA double-strand break (DSB) end resection and CCF formation.

42 ls also exhibit reduced double-strand break (DSB) formation and increased survival upon replication s

43 mal requirement for DNA double-strand break (DSB) formation is as low as even one AID deamination eve

44 eficient cells involved double-strand break (DSB) formation, in this case by the SLX4/SLX1 nuclease.

45 ion of an enzyme-linked double-strand break (DSB) in one DNA molecule and passage of another intact D

46 comes of a Cas9-induced double-strand break (DSB) introduced on the paternal chromosome at the EYS lo

47 To determine whether double-strand break (DSB) mobility enhances the physical search for an ectopi

48 fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent

49 otype that enhances DNA double-strand break (DSB) persistence to enhance detection.

50 2 was implicated in DNA double strand break (DSB) repair and in resolving replication stress.

51 lays or failure of rDNA double-strand break (DSB) repair are deleterious, and can lead to rDNA transc

52 leads to defects in DNA double-strand break (DSB) repair by homologous recombination (HR) and renders

53 in (BRCA1) promotes DNA double-strand break (DSB) repair by homologous recombination and protects DNA

54 in responses during DNA double-strand break (DSB) repair have been studied with biochemistry or as in

55 The early steps of DNA double-strand break (DSB) repair in human cells involve the MRE11-RAD50-NBS1

56 Tracking DNA double strand break (DSB) repair is paramount for the understanding and thera

57 to master regulator of double-strand break (DSB) repair pathway choice.

58 tive will highlight DNA double-strand break (DSB) repair pathways in human cells, how DNA repair fail

59 rk progression, and DNA double-strand break (DSB) repair.

60 editing outcomes after double strand break (DSB) repair.

61 the accumulation of DNA double-strand break (DSB) response factors.

62 yields for plasmid and Double Strand Break (DSB) yields for plasmid/human cell.

63 amma-H2AX) around a DNA double-strand break (DSB).

64 y that identified the double-stranded break (DSB) repair and Fanconi anemia (FA) factors active in th

65 lates a DDR choice in double-stranded break (DSB) repair.

66 een the Cas9-mediated double-stranded break (DSB) to the mutation site, rather than DSB efficiency, w

67 DNA double-strand breaks (DSB) are the most deleterious type of DNA damage.

68 Repair of DNA double-strand breaks (DSB) is performed by two major pathways, homology-depend

69 Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification

70 ces subjected to double-stranded DNA breaks (DSBs) made by programmable nucleases (e.g. CRISPR-Cas9).

71 5-fold increase in double-strand DNA breaks (DSBs) throughout meiotic prophase I and a concurrent red

72 zing and repairing double-strand DNA breaks (DSBs) via non-homologous end joining.

73 DNA repair factors to double-strand breaks (DSBs) after genome editing with CRISPR nucleases.

74 meric and subtelomeric double-strand breaks (DSBs) and increase VSG switching rate.

75 he repair of telomeric double-strand breaks (DSBs) and induced ALT-like phenotypes, including ALT-ass

76 DNA double-strand breaks (DSBs) are common genome lesions that threaten genome sta

77 DNA double-strand breaks (DSBs) are highly cytotoxic lesions that can lead to chro

78 DNA double-strand breaks (DSBs) are implicated in various physiological processes,

79 intergenic areas when double-strand breaks (DSBs) are induced.

80 sover, hundreds of DNA double-strand breaks (DSBs) are introduced in the genome of each meiotic cell

81 DNA double-strand breaks (DSBs) are toxic to mammalian cells.

82 h the formation of DNA double-strand breaks (DSBs) at specific genomic locations that correspond to P

83 PR (vfCRISPR), creates double-strand breaks (DSBs) at the submicrometer and second scales.

84 L3 is recruited to DNA double-strand breaks (DSBs) by PARP1 at an early time point, which requires it

85 mediated mutations and double-strand breaks (DSBs) by perturbing canonical base excision repair (BER)

86 on, critical to repair double-strand breaks (DSBs) by recombination, is not well understood, particul

87 HEJ) for the repair of double-strand breaks (DSBs) caused by reactive oxygen species.

88 During meiosis, DNA double-strand breaks (DSBs) enter interhomolog repair to yield crossovers and

89 stress markers and DNA double-strand breaks (DSBs) in cells depleted for Topoisomerase I (Top1), an e

90 In many vertebrates, double-strand breaks (DSBs) initiate recombination within hotspots where PRDM9

91 The number of DNA double-strand breaks (DSBs) initiating meiotic recombination is elevated in Sa

92 fficient repair of DNA double-strand breaks (DSBs) is of critical importance for cell survival.

93 tein RAD51 to sites of double-strand breaks (DSBs) or the abundance of proteins associated with RF in

94 DNA double-strand breaks (DSBs) pose an everyday threat to the conservation of gen

95 nts and programmed DNA double-strand breaks (DSBs) promote homologue pairing and initiate recombinati

96 fficient repair of DNA double-strand breaks (DSBs) requires a coordinated DNA Damage Response (DDR),

97 of CRISPR/Cas9-induced double strand breaks (DSBs) revealed that long-stem hairpin-forming sequences

98 rate that DNA nicks or double-strand breaks (DSBs) targeted by CRISPR-Cas9 to both homologs can stimu

99 The repair of DNA double strand breaks (DSBs) that arise from external mutagenic agents and rout

100 domly distributed, the double-strand breaks (DSBs) that initiate recombination are not located arbitr

101 DNA damage, including double strand breaks (DSBs) that interfere with replication.

102 e method for analyzing double-strand breaks (DSBs) that we apply in parallel to eight Cas9 variants a

103 in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protei

104 is study, multiple DNA double-strand breaks (DSBs) were generated via the CRISPR/Cas9 system at centr

105 (SSBs), but not direct double-strand breaks (DSBs), in the genome during gene activation by ligands o

106 which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct

107 ch lack endogenous DNA double-strand breaks (DSBs), to induce a single DSB by Mos1 transposon excisio

108 CLs without generating double-strand breaks (DSBs), unlike the FA/BRCA pathway.

109 Mtb strain, Rv caused double strand breaks (DSBs), whereas the non-virulent Ra strain triggered sing

110 of DNA damage are DNA double-strand breaks (DSBs), which can cause cell lethality if unrepaired or c

111 tened by cytotoxic DNA double-strand breaks (DSBs), which must be resolved efficiently to prevent seq

112 lar sensitivity to DNA double-strand breaks (DSBs).

113 tiation via programmed double-strand breaks (DSBs).

114 els in response to DNA double-strand breaks (DSBs).

115 age response after DNA double-strand breaks (DSBs).

116 iated by SPO11-induced double-strand breaks (DSBs).

117 age, specifically, DNA double-strand breaks (DSBs).

118 pair of programmed DNA double-strand breaks (DSBs).

119 em, used to target DNA double-strand breaks (DSBs).

120 A) is regulated at DNA double-strand breaks (DSBs).

121 directed repair of DNA double-strand breaks (DSBs).

122 ion (HR) repair of DNA double strand breaks (DSBs).

123 iginating from meiotic double-strand breaks (DSBs).

124 breaks (SSBs) and DNA double-strand breaks (DSBs); lesions that can trigger neurodegeneration and ne

125 DNA double-stranded breaks (DSBs) are dangerous lesions threatening genomic stabilit

126 DNA double-stranded breaks (DSBs) are strongly associated with active transcription,

127 DNA double-stranded breaks (DSBs) trigger human genome instability, therefore identi

128 cient in joining DNA double-stranded breaks (DSBs) with hairpinned termini.

129 repair (HRR) of DNA double-stranded breaks (DSBs).

130 de DSB identification approach that captures DSBs via their ability to join to specific genomic Cas9/

131 host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor).

132 nsposable elements, which are known to cause DSBs and alter genome integrity [6, 7].

133 In Top1-depleted cells, DSBs also accumulate at TTS, leading to persistent check

134 Laser-induced clustered DSBs led to global compaction of even the undamaged chro

135 in elucidating the balance between competing DSB repair pathways.

136 nstrate that Polmu may address complementary DSB substrates during NHEJ in a manner indistinguishable

137 er, endonucleases that simultaneously create DSBs in multiple defined and unique loci of the yeast ge

138 ired for efficient repair of PRDM9-dependent DSBs and for pairing of homologous chromosomes in male m

139 e only polyphenols transported from digested DSB.

140 to dissecting the contributions of distinct DSB sensors in downstream signaling.

141 s a model system to specifically mimic a DNA DSB, enabling us to study the end-joining of two fluores

142 ealed that these variants did not affect DNA DSB end resection efficiency.

143 y by proteolytic degradation followed by DNA DSB repair.

144 nclude that an in-depth understanding of DNA DSB repair pathways in human cells will lead to novel th

145 In response to DNA DSBs, cells activate a complex DNA damage checkpoint (DD

146 facilitate tightly controlled and efficient DSB formation at defined genomic sites and will be valua

147 When cells encounter DSBs in interphase, they are able to arrest the cell cyc

148 ndary structures are enriched for endogenous DSBs in human cells.

149 ossible physiological consequences of failed DSB responses in mitosis.

150 plained solely by their structural features (DSB focus size, local chromatin compaction).

151 ted CDDR (CRISPR-Cas9-based Dual-fluorescent DSB Repair), that enables the detection and quantificati

152 el-like structure that has high affinity for DSB.

153 BLRR analysis detected altered dynamics for DSB repair induced by small-molecule modulators.

154 precise, sensitive, and universal method for DSB detection, to enable both the study of their mechani

155 However, HELLS is not required for DSB activity at PRDM9-independent sites.

156 It activates downstream signaling for DSB repair by triggering ATM recruitment, H2AX phosphory

157 ript or a DNA copy of the RNA transcript for DSB repair, respectively, and a new mechanism of RNA-tem

158 leading to the liberation of a protein-free DSB.

159 ermediates clustered near to but offset from DSB positions, consistent with joint molecules with inco

160 to rDNA sequences in response to both global DSBs generated by IR and site-specific DSBs in rDNA.

161 us especially when working with slow growing DSB repair mutants.

162 icated repair machineries to detect and heal DSBs.

163 In male mice lacking HELLS, DSBs are retargeted to other sites of open chromatin, le

164 ion and provide insight into how homeostatic DSB controls respond to aneuploidy during meiosis.

165 However, DSB-3 is not widely available and also reacts with PSD's

166 r, we did not detect a significant defect in DSB repair (DSBR) in primary fibroblasts from PNKP patie

167 mplex is destabilized, leading to defects in DSB repair, homolog synapsis, and crossover formation.

168 ate that, rather than being deterministic in DSB repair pathway choice, 53BP1 functions as a DSB esco

169 identified mutations in 31 genes involved in DSB response and repair.

170 Polymerase mu (Polmu) participates in DSB repair via the nonhomologous end-joining (NHEJ) path

171 binding sites, and uncovered an increase in DSBs at highly stable DNA secondary structure regions, i

172 nd human leads to a significant reduction in DSBs at structure-prone loci, and that sites of TOP2 cle

173 mutants ecm11 and gmc2 experienced increased DSB numbers diagnostic of homolog engagement defects.

174 Cells from Mecp2/Y mice have increased DSBs, so this finding suggests that the balance between

175 bit; therefore, the observation of increased DSBs with increasing drug doses at pausing sites indicat

176 In addition, the yields of indirect DSBs are compatible with the experimental scavengeable d

177 NA recombination with and without an induced DSB in yeast DNA, we characterize three forms of RNA-med

178 revealing that cells respond to Cas9-induced DSBs within minutes and can retain MRE11 after DNA ligat

179 We demonstrate that these heat-induced DSBs in spermatocytes are independent of the endonucleas

180 nd that the production of these heat-induced DSBs in spermatocytes correlate with heat-induced mobili

181 Ionizing radiation (IR)-induced DSBs lead to the same outcomes, and modeling of IR dose-

182 horylated H2AX at ionizing radiation-induced DSBs but not with 53BP1.

183 e have generated a single specific inducible DSB in the cells and systematically examined the histone

184 lack a negative feedback loop that inhibits DSB formation when homologs engage one another.

185 i-BLESS labels DSBs with single-nucleotide resolution, allows detection

186 , providing an intrinsic mechanism for local DSB formation, which is a strong inducer of VSG switchin

187 compaction changes in response to localized DSBs directly.

188 , but also suppresses the gammaH2AX-mediated DSB response.

189 In yeast, the Rad52 protein mediates DSB repair via homologous recombination.

190 rgeting, and the ATM kinase controls meiotic DSB numbers.

191 of DSB-adjacent DNA is a key step in meiotic DSB repair, but this process has remained understudied.

192 T pathway, and consequently promotes meiotic DSB repair and homologous recombination.

193 Meiotic DSBs are generated by Spo11 and accessory DSB proteins,

194 nt is associated with suppression of meiotic DSBs and crossovers at the chromosome and fine scales.

195 demonstrate the direct detection of meiotic DSBs and resection using END-seq on mouse spermatocytes

196 If left unrepaired, meiotic DSBs can cause aneuploidy in gametes and compromise viab

197 Moreover, DSBs were not detected after therapy when apoptosis was

198 Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its ch

199 l restriction enzymes for single or multiple DSB formation, respectively.

200 Multiple DSBs initiate recombination, and most are repaired witho

201 The roles of these proteins in nucleolytic DSB resection are well characterized, but their role in

202 B) competition dataset, three users obtained DSB score of 0.331 +/- 0.006.

203 he physiology and therapeutic development of DSB repair.

204 Fidelity of DSB repair is best achieved by recombination with a homo

205 porter (BLRR) for non-invasive monitoring of DSB repair pathways in living cells and animals.

206 How the nonrandomness of DSB distributions is controlled is not understood, altho

207 and potentially other mutagenic pathways of DSB repair.

208 rtant players in the SSA and BIR pathways of DSB repair.

209 enables the detection and quantification of DSB repair outcomes in mammalian cells with high precisi

210 The nucleolytic resection of DSB-adjacent DNA is a key step in meiotic DSB repair, bu

211 Our findings place SIRT6 as a sensor of DSB, and pave the road to dissecting the contributions o

212 nome are not available, hindering studies of DSB repair in different genomic regions and chromatin co

213 Accumulation of DSBs mediated through Rv activates ATM-Chk2 pathway of D

214 Mapping the distribution of DSBs along actively expressed genes and identifying the

215 e processing of DNA ends and the dynamics of DSBs.

216 aturation of the PAR structure, formation of DSBs and completion of pairing and synapsis.

217 duction is associated with the generation of DSBs, the repair of which is likewise essential for the

218 re essential and adequate for the genesis of DSBs.

219 ressed genes and identifying the location of DSBs relative to pausing sites can provide mechanistic i

220 regulate the timing, location and number of DSBs.

221 played only a back-up role in the repair of DSBs performing an error-prone single strand annealing (

222 promotes DSB formation and biases repair of DSBs to homologs over sister chromatids.

223 , permitting correct placement and repair of DSBs.

224 rdered protein RBM14 for efficient repair of DSBs.

225 edited cells can lose fitness as a result of DSBs at allelic and non-allelic target sites and report

226 To see whether enhanced HDR depends on DSB mobility or the global chromatin response, we tested

227 repair pathway choice between NHEJ and other DSB repair pathways.

228 Moreover, we demonstrate that PALB2 DSB recruitment in BRCA1/53BP1-deficient cells is mediat

229 Persistent DSBs in Brme1(-/-) reactivate the somatic-like DNA-damag

230 ve rise to DSBs indirectly, but also promote DSB repair by inducing R-loops, revealing an unexpected

231 TPase domain of HELLS is required to promote DSB repair.

232 us chromosomes during prophase that promotes DSB formation and biases repair of DSBs to homologs over

233 rt the hypothesis that SC formation provokes DSB protein dissociation, leading in turn to loss of a D

234 Inhibiting GLI1 interferes with rDNA DSB repair and impacts RNA polymerase I activity and cel

235 pathway, is required for the repair of rDNA DSBs.

236 al axis structures form in rec8 that recruit DSB-associated protein foci and undergo synapsis, which

237 utes a negative feedback loop that regulates DSB repair.

238 ed multiple mechanisms to efficiently repair DSBs to preserve genomic integrity.

239 atic-like DNA-damage response, which repairs DSBs but cannot complement the crossover formation defec

240 Here, we define structures of resected DSBs in mouse spermatocytes genome-wide at nucleotide re

241 thogen Cryptococcus neoformans The resulting DSBs were repaired in a complex manner, leading to the f

242 assembly at the damaged chromatin and shifts DSB repair to mutagenic NHEJ, revealing a backup functio

243 c because the observed dynamical signatures (DSB mobility) can be explained solely by their structura

244 cleases are commonly used to create a single DSB at a unique cleavage site.

245 ble-strand breaks (DSBs), to induce a single DSB by Mos1 transposon excision at defined chromosomal l

246 Moreover, other Sirtuins share some DSB-binding capacity and DDR activation.

247 We induced a site-specific DSB with HO endonuclease at the MAT locus on chromosome

248 lobal DSBs generated by IR and site-specific DSBs in rDNA.

249 lly useful for the evaluation of spontaneous DSB levels and the estimation of DNA damage induced rath

250 ic sites and will be valuable tools to study DSB repair at a local and genome-wide scale.

251 To study DSB repair pathways and associated factors, inducible si

252 in vivo infection with Mtb led to sustained DSBs and ATM activation during chronic phase of tubercul

253 DAXX deficiency recapitulates all telomeric DSB repair phenotypes associated with ATRX loss.

254 reveal that ATRX has an effect on telomeric DSB repair and that this role involves both telomere coh

255 rmation in cells with FokI-induced telomeric DSBs and in alternative lengthening of telomeres (ALT) c

256 he efficient repair of ROS-induced telomeric DSBs.

257 BIR of telomeric DSBs competed with PARP1-, LIG3-, and XPF-dependent alte

258 arise from BIR-mediated repair of telomeric DSBs.

259 t a role for DAXX in the repair of telomeric DSBs.

260 yeast, transcript RNA was shown to template DSB repair of DNA.

261 nomic modifications: RNA- and cDNA-templated DSB repair (R-TDR and c-TDR) using an RNA transcript or

262 reak (DSB) to the mutation site, rather than DSB efficiency, was the primary determinant for successf

263 ng that global histone depletion rather than DSB movement is rate limiting for HDR.

264 Our findings show that DSB number is regulated in a chromosome-autonomous fashi

265 Extensive evidence shows that DSBs are a primary source of chromosome translocations o

266 Collectively, data suggests that DSBs inflicted by SecA2 secretome of Mtb provides surviv

267 and distribution of modification around the DSB are significantly different.

268 SBs and their local environment, such as the DSB focus size (represented by the local accumulation of

269 not the major 5' -> 3' exonuclease, but the DSB-responsive kinase ATM proved a key regulator of both

270 ing-disk confocal microscopy, we monitor the DSB dynamics and the compaction of the surrounding chrom

271 OP2 (TOP2 poisons) prevent religation of the DSB and stabilize a normally transient intermediate of t

272 microhomology upstream and downstream of the DSB.

273 mology that is embedded from the edge of the DSB.

274 resection, which we find is dependent on the DSB end protection factor KU.

275 utant show a weakened ability to sustain the DSB response compared with those expressing WT SMURF2 fo

276 Our findings reveal that the DSB mobility follows a universal relationship defined so

277 Moreover, our data show that the DSB motion is subdiffusive and ATP-dependent and exhibit

278 This suggests that the DSB-related repair processes are robust and likely deter

279 ck inversions when proximal or distal to the DSB, whereas short-stem hairpin-forming sequences formed

280 t are brought into physical proximity to the DSB.

281 med foldback inversions when proximal to the DSB.

282 ly by the physical parameters describing the DSBs and their local environment, such as the DSB focus

283 at, like CNTD1, PRR19 is required for timely DSB repair and the formation of crossover-specific recom

284 efore identifying what factors contribute to DSB induction is critical for our understanding of human

285 to track the precise recruitment of MRE11 to DSBs by chromatin immunoprecipitation followed by next-g

286 but not the latter is altered in response to DSBs.

287 Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away

288 ced telomeric SSBs may not only give rise to DSBs indirectly, but also promote DSB repair by inducing

289 de leads to persistent and potentially toxic DSBs.

290 and more frequent translocations between two DSBs.

291 hway to repair psoralen-ICL through a unique DSB-free mechanism in human cells.

292 tants, even when the abundance of unresolved DSBs is high.

293 mologous end joining (NHEJ) is the most used DSBs repair pathway in the cells, how NHEJ factors are s

294 Using an in vivo DSB repair pathway assay, we find that Ino80 is selectiv

295 However, when DSBs occur during mitosis, cells no longer arrest but pr

296 s inhibited, supporting a framework in which DSBs are not directly induced by genotoxic agents, but r

297 Oocytes in which DSBs persist are therefore eliminated by the DNA-damage

298 tly developed ultrasensitive and genome-wide DSB detection method: immobilized direct in situ breaks

299 We tested for RDCs by our genome-wide DSB identification approach that captures DSBs via their

300 Consistent with DSB induction, we found that the DNA damage and stress r