ライフサイエンスコーパス: fragile site

1 ncogene BCL2 as a replication stress-induced fragile site.

2 structure of breakpoint regions in a common fragile site.

3 ene, like FHIT and WWOX, located at a common fragile site.

4 emonstration of a germline break in a common fragile site.

5 e, and this locus becomes a folate-sensitive fragile site.

6 ation that encompasses the FRA3B chromosomal fragile site.

7 2 genes in generating a novel Ad12-inducible fragile site.

8 genes would generate a novel Ad12-inducible fragile site.

9 suffice to generate a new virally inducible fragile site.

10 s would also generate a novel Ad12-inducible fragile site.

11 ns in known CFSs and identification of novel fragile sites.

12 dividuals and represent the largest class of fragile sites.

13 acteristics similar to those in other common fragile sites.

14 n to result in chromosome breakage at common fragile sites.

15 ith the presence of previously mapped common fragile sites.

16 a foundation to understand the expression of fragile sites.

17 e in cancer-associated genomic regions or in fragile sites.

18 romatin, gene dense regions, and chromosomal fragile sites.

19 DNA replication induce expression of common fragile sites.

20 egions are the most characteristic of common fragile sites.

21 eviously identified candidate genes or known fragile sites.

22 nd late-replicating loci such as chromosomal fragile sites.

23 ting a common mechanism for the formation of fragile sites.

24 aberrations often involve regions containing fragile sites.

25 been observed for several of the cloned rare fragile sites.

26 collapse, late origin firing and stabilizes fragile sites.

27 ution view of replication-associated genomic fragile sites.

28 omotes replication of DNA lesions and common fragile sites.

29 activity and reduced chromosomal breakage at fragile sites.

30 give rise to distinct patterns of chromosome fragile sites.

31 dary structures that are hallmarks of common fragile sites.

32 that we detected correlated with cytogenetic fragile sites.

33 of lost regions located in genes and common fragile sites.

34 e the preference of HPV for integration into fragile sites.

35 ress generated unrepaired breaks and SCEs at fragile sites.

36 condary structures has not been evaluated in fragile sites.

37 res, telomeres, evolutionary breakpoints and fragile sites.

38 rate that OPT domains are enriched at common fragile sites.

39 The second factor is that telomeres are fragile sites.

40 Poleta in replicating through D loop and DNA fragile sites.

41 us deletions over recessive cancer genes and fragile sites.

42 resemble those of aphidicolin-induced common fragile sites.

43 and chromosomal breakage at the accompanying fragile sites.

44 e hamster ovary (CHO) cell line, breakage at fragile site 1q31 was associated with mdr1 gene amplific

45 Fragile site 2 (FS2) is a naturally occurring IR in Sacc

46 y to retain intact fragile common chromosome fragile site 3B(FRA3B)/FHITloci.

47 his leads to formation of gaps and breaks at fragile sites, 4N accumulation, and aberrant cell divisi

48 ral molecular mechanism for the formation of fragile sites, a different class of fragile site, the 33

49 leted region at D6S1045 is not the result of fragile sites, a recombination hot spot, or a feature of

50 ation, non-homologous end-joining and genome fragile sites all have potential roles in the production

51 FRA3B thus fulfills the prophecy that fragile site alterations contribute to the neoplastic pr

52 uch breakpoints, however, map distal to this fragile site and are not linked with its expression.

53 and asked whether it also contains a common fragile site and if it is unstable in mouse tumors or tu

54 he tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental

55 agent, a clastogen, a mutagen, an inducer of fragile sites and a carcinogen.

56 w-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas.

57 ion, have been found to frequently reside in fragile sites and genomic regions associated with cancer

58 evant to chromosome instability of mammalian fragile sites and of chromosomes in cancer cells.

59 nce indicates that telomeres resemble common fragile sites and present a challenge for DNA replicatio

60 RC sites are strongly associated with common fragile sites and recurrent deletions in cancers.

61 ication stress, certain loci, such as common fragile sites and telomeres, remain under-replicated dur

62 ad of the fork, including stable protein-DNA fragile sites and termination.

63 Extreme late replication is a property of fragile sites and the 21-kb deletions destabilized the D

64 been learned about the genomic structure at fragile sites and the cellular checkpoint functions that

65 understanding the genomic features of common fragile sites and the cellular processes that monitor an

66 Fragile sites and their associated genes show frequent d

67 addition, important genomic elements such as fragile sites and tRNA genes are found to be clustered s

68 s the most frequently expressed human common fragile site, and allelic losses at FRA3B have been obse

69 ve cancer genes, 17 were of sequenced common fragile sites, and 178 were in genomic regions that do n

70 ntially located at late-replicating domains, fragile sites, and breakpoints, including the mixed-line

71 r results may account for the role of LTR in fragile sites, and for the association of CENP-B with pe

72 Fragile sites appear as breaks, gaps, or decondensations

73 Common fragile sites appear to arise through incomplete DNA rep

74 Implicit in this hypothesis is that genes at fragile sites are altered by chromosome rearrangement an

75 Folate-sensitive fragile sites are associated with the expansion and hype

76 Fragile sites are gaps and breaks in metaphase chromosom

77 Chromosomal fragile sites are genomic loci sensitive to replication

78 Common fragile sites are highly unstable regions of the genome.

79 gous deletions of recessive cancer genes and fragile sites are known to occur in human cancers.

80 Common fragile sites are loci that form chromosome gaps or brea

81 In contrast, common fragile sites are present in all individuals and represe

82 Fragile sites are prone to deletions, translocations, an

83 important in fragile-site stability and that fragile sites are recognized by the G(2)/M checkpoint pa

84 Several lines of evidence suggest that fragile sites are regions of DNA whose replication is un

85 Common fragile sites are regions of human chromosomes prone to

86 Several lines of evidence suggest that fragile sites are regions of late replication.

87 Human chromosomal fragile sites are regions of the genome that are prone t

88 Common fragile sites are regions that show elevated susceptibil

89 Rare fragile sites are seen in a small proportion of individu

90 Human chromosomal fragile sites are specific loci that are especially susc

91 Chromosomal fragile sites are specific loci that preferentially exhi

92 Common fragile sites are specific regions in the human genome t

93 Common fragile sites are specific regions of the genome that fo

94 Thus, we propose that fragile sites are unreplicated chromosomal regions resul

95 Human fragile sites are weak staining gaps in chromosomes gene

96 Specific regions of genomes (fragile sites) are hot spots for the chromosome rearrang

97 Common fragile sites, as their name implies, are present in vir

98 how that miR genes are frequently located at fragile sites, as well as in minimal regions of loss of

99 lutionarily conserved novel gene, designated fragile site-associated (FSA) gene.

100 HIT encompasses the common human chromosomal fragile site at 3p14.2 and numerous cancer cell bialleli

101 IT, encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal cancer tran

102 FRA7G is a common aphidicolin-inducible fragile site at 7q31.2, showing loss of heterozygosity i

103 The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a tumor suppressor

104 mere replication was compromised, leading to fragile sites at telomeres.

105 reakpoint region (Mbr) on chromosome 18 is a fragile site, because it adopts a non-B DNA conformation

106 ls with low doses of aphidicolin that induce fragile site breakage.

107 destabilized chromosomes and specific common fragile site breakage.

108 provide insight not only into the nature of fragile sites, but also into the broader consequences of

109 lication underlies fragility at common human fragile sites, but specific sequences responsible for ex

110 erved functional elements within orthologous fragile sites by interspecies sequence comparison.

111 the first to demonstrate that AT islands in fragile sites can function as MARs both in vitro and in

112 Thus, the study of common fragile sites can provide insight not only into the natu

113 ormal demonstration that certain chromosomal fragile sites can serve as RAG complex targets, and they

114 e cloning and characterization of the common fragile site (CFS) FRA6E (6q26) identified Parkin, the g

115 Common fragile sites (CFS) are chromosomal regions that exhibit

116 RFS), while ERFS and late-replicating common fragile sites (CFS) are equally fragile in response to a

117 though distinct from late-replicating common fragile sites (CFS), the stability of ERFSs and CFSs is

118 -to-replicate genomic regions, namely common fragile sites (CFS).

119 ith DNA secondary structures, such as common fragile sites (CFSs) and palindromic repeats.

120 Chromosomal common fragile sites (CFSs) are genetically unstable regions of

121 Common fragile sites (CFSs) are genomic regions prone to breaka

122 Common fragile sites (CFSs) are genomic regions that are unstab

123 Common fragile sites (CFSs) are hot spots of chromosomal breaka

124 Common fragile sites (CFSs) are large genomic regions present i

125 Common fragile sites (CFSs) are loci that preferentially exhibi

126 Common fragile sites (CFSs) are regions of profound genomic ins

127 Common fragile sites (CFSs) are regions susceptible to replicat

128 Chromosomal common fragile sites (CFSs) are unstable genomic regions that b

129 ves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA

130 rvical cancer and the position of the common fragile sites (CFSs) has been observed at both the cytog

131 rvical cancer and the position of the common fragile sites (CFSs) has been observed at the cytogeneti

132 Common fragile sites (CFSs) represent large, highly unstable re

133 enomic deletions and duplications and common fragile sites (CFSs) seen as breaks on metaphase chromos

134 metaphase telomeres that resemble the common fragile sites (CFSs), and the association of sister telo

135 is also required for the stability of common fragile sites (CFSs), whose rearrangements are considere

136 le telomeres-structures that resemble common fragile sites (CFSs)-but how they are formed is not know

137 y integrates at loci containing human common fragile sites (CFSs).

138 nsitive RFSs share many features with common fragile sites (CFSs; which are found in all individuals)

139 regions, we assessed the stability of common fragile sites, chromosomal loci that are prone to breaka

140 Thus, this is the largest common fragile site cloned to date.

141 With three common fragile sites cloned, their mechanism of expression and

142 found that aphidicolin (APH)-induced common fragile sites contain more sequence segments with potent

143 FRA7G is a common fragile site containing the candidate tumor suppressor g

144 Moreover, this fragile site contains an evolutionarily conserved novel

145 nearest transcription start site, chromosome fragile sites, CpG islands, viral sequences and target s

146 Fragile site damage is thought to arise from the aberran

147 Common chromosomal fragile sites, defects in DNA replication or telomere dy

148 ible for aphidicolin-induced and FdU-induced fragile sites differ.

149 B-mediated DNA amplification, we cloned 1q31 fragile site DNA from a Chinese hamster cell line contai

150 In this study, loss of expression of the fragile site-encoded Wwox protein was found to contribut

151 ion induces more breaks at early replicating fragile sites (ERFS), while ERFS and late-replicating co

152 endent DNA lesions, termed early replication fragile sites (ERFSs), by genome-wide localization of DN

153 st genetic condition in mammals that reduces fragile site expression and alleviates the severity of a

154 Yet, the mechanism of fragile site expression has been elusive.

155 ATR deficiency results in fragile site expression with and without addition of rep

156 prevent mitotic catastrophe following common fragile site expression.

157 down by RNA interference, also have elevated fragile-site expression.

158 at ATR-deficient cells have greatly elevated fragile-site expression.

159 This fragile site extends over a broad region of several hund

160 ted with increased chromosome instability at fragile sites following replication stress, and these fi

161 Common fragile sites form gaps at characteristic chromosome ban

162 ion within the human genome is able to drive fragile site formation under conditions of replication s

163 Given its similarity to known chromosomal fragile site (FRA) sequences, this polymorphic 1p21.2 se

164 ET/PTC rearrangements, are located in common fragile sites FRA10C and FRA10G, and undergo DNA breakag

165 ap of a previously published rare, heritable fragile site, FRA11A, with the cervical cancer deletion

166 trinucleotide repeat at the folate-sensitive fragile site FRA11B has been implicated in the generatio

167 AT islands in fragile sites FRA16B and FRA16D are significantly more a

168 umor suppressor gene that maps to the common fragile site FRA16D on chromosome 16q23.3-24.1, is alter

169 ning of WWOX, a gene that maps to the common fragile site FRA16D region in chromosome 16q23.3-24.1.

170 WWOX may span the yet uncharacterized common fragile site FRA16D region.

171 Fragile site FRA16D spans the WWOX/FOR tumor suppressor

172 WOX gene, encompassing the common chromosome fragile site FRA16D, is altered in a large fraction of c

173 OX, the gene that maps to common chromosomal fragile site FRA16D, is frequently affected by aberratio

174 1, a chromosome region that spans the common fragile site FRA16D.

175 r suppressor spanning the common chromosomal fragile site FRA16D.

176 f >1 Mb across the second most active common fragile site, FRA16D (16q23.2).

177 ontaining oxidoreductase) gene at the common fragile site, FRA16D, is altered in many types of cancer

178 The 16q23.2 breakpoint transects the common fragile site, FRA16D, providing a molecular demonstratio

179 ressor spanning the second most common human fragile site, FRA16D.

180 g agent and was able to induce 5azaC-dR type fragile sites FRA1J and FRA9E in human cells.

181 Fragile site FRA3B is the most unstable site and is dire

182 The FHIT gene, which spans the common fragile site FRA3B, has been shown to produce aberrant t

183 The fragile site FRA3B, which lies within the FHIT tumor-sup

184 in a variety of tumors and spans the common fragile site FRA3B.

185 and breaks and breaks at the specific common fragile sites FRA3B and FRA16D were significantly elevat

186 triad gene (FHIT) encompasses a human common fragile site, FRA3B, that is susceptible to environmenta

187 d in the fragility of the most active common fragile site, FRA3B.

188 the FHIT gene, which encompasses the common fragile site, FRA3B.

189 at the DNA probe for D7S522 spans the common fragile site FRA7G at 7q31.

190 the MET amplicon in these EAs is defined by fragile site FRA7G.

191 suppressor locus (7q31.1/D7S522) and a known fragile site (FRA7G) that is deleted in a variety of epi

192 Thus for the first two cloned common fragile sites, FRA7G and FRA3B, there is an association

193 Common fragile sites frequently coincide with the location of g

194 construct a statistical model that separates fragile sites from regions showing signatures of positiv

195 We find that the LMO2 fragile site functions as a 12-signal at an efficiency t

196 esults suggest that the Chinese hamster 1q31 fragile site has many important functions including regu

197 repeating DNA derived from folate-sensitive fragile sites has been shown to exclude single nucleosom

198 The study of common fragile sites has its roots in the early cytogenetic inv

199 esponsible for expression of these inducible fragile sites have not been identified.

200 cycle checkpoints and DNA repair, and common fragile sites have provided insight into understanding t

201 ng component of chromosome structure, common fragile sites have taken on novel significance as region

202 ng component of chromosome structure, common fragile sites have taken on novel significance as region

203 The fragile site in 11q23.3, FRA11B, has been shown to cause

204 which contains the most common constitutive fragile site in the genome, FRA3B.

205 the second most common aphidicolin-inducible fragile site in the human genome (Fra7G).

206 osomal band 3p14.2 is the most active common fragile site in the human genome.

207 of this 363 bp segment effectively creates a fragile site in the micronuclear genome, providing the f

208 e frequency of double-strand breaks (DSB) at fragile sites in cancer cells due to replication stress.

209 ing proteins could lead to rearrangements at fragile sites in cancer cells.

210 increased instability at common chromosomal fragile sites in cells lacking the replication checkpoin

211 ot for chromosome aberrations reminiscent of fragile sites in human cells.

212 FRAXA is one of a number of fragile sites in human chromosomes that are induced by a

213 We found that several major chromosomal fragile sites in human lymphomas, including the bcl-2 ma

214 We previously identified two chromosome fragile sites in Saccharomyces cerevisiae that were indu

215 t Ad12 cannot induce the RNU1, RNU2, or PSU1 fragile sites in Saos-2 cells lacking the p53 and retino

216 Here, we studied the involvement of fragile sites in the formation of RET/PTC rearrangements

217 evidence for the involvement of chromosomal fragile sites in the generation of cancer-specific rearr

218 nderlying most of the known folate-sensitive fragile sites in the genome.

219 B at 3p14.2 is the most active of the common fragile sites in the human genome and is expressed when

220 maps to FRA6E, one of the most active common fragile sites in the human genome, it represents another

221 s stress but also in its absence, similar to fragile sites in the human genome.

222 ene deficiencies and induction of chromosome fragile sites in vitro, we have analyzed the frequency o

223 To determine whether CGG tracts are fragile sites in yeast, the CGG tracts were flanked by d

224 ter chromosomal instability, particularly at fragile sites, in SCKL1-affected patient cells after tre

225 In contrast to the rare fragile sites, including FRAXA, no repeat motifs, such a

226 , and undergo DNA breakage after exposure to fragile site-inducing chemicals.

227 entify FRA3B sequences that are required for fragile site induction, we used microcell-mediated chrom

228 f ssDNA associated with disruption of genome fragile sites, inefficient cell cycle progression, and i

229 ions for understanding both the mechanism of fragile site instability and the consequences of stalled

230 stress accompanied by dramatic increases in fragile site instability, and chromosomal amplifications

231 duced replication intermediates, suppressing fragile site instability, and localizing SLX4 to ALT tel

232 e role of DNA secondary structures in common fragile site instability, provides a systematic method f

233 To understand the mechanism of fragile site instability, we examined the contribution o

234 de fusion with interstitial loci adjacent to fragile sites, intra-molecular rearrangements, and fusio

235 dings demonstrate that SCE-FISH frequency at fragile sites is a sensitive indicator of replication st

236 DNA breakage at fragile sites is associated with regions that are delete

237 Further, the fragile site-like nature of all of the breakpoint sites

238 RA3B is the most frequently expressed common fragile site localized within human chromosomal band 3p1

239 ian tumors, indicating that loss within this fragile site may be important in the development or prog

240 The hypothesis that chromosomal fragile sites may be "weak links" that result in hot spo

241 is work further demonstrates that the common fragile sites may play an important role in cancer devel

242 Recent findings suggest that common fragile sites may serve as markers of chromosome damage

243 Correspondingly, genes at common fragile sites may sustain elevated levels of DNA damage

244 expansion of 55-200 CGG repeats in the FMR1 (fragile site mental retardation 1) gene.

245 e associated with cancer breakpoints, common fragile sites, microRNA, and cancer-related genes, sugge

246 test the hypothesis that other unidentified fragile sites might be located in 11q23.3-24 and may cau

247 Furthermore, SCEs were suppressed at fragile sites near centromeres in response to replicatio

248 Chromosomal fragile sites not only are susceptible to DNA instabilit

249 replication is compromised, analogous to the fragile sites observed in mammalian chromosomes.

250 d is the most highly expressed of the common fragile sites observed when DNA replication is perturbed

251 2 is the most highly expressed of the common fragile sites observed when DNA replication is perturbed

252 ces demonstrated that gaps and breaks in the fragile site occur over a broad region within and proxim

253 12 interval known to contain the most common fragile site of the human genome (FRA3B), the FHIT gene,

254 e 3p14.2 region spans the most active common fragile site of the human genome, encompassing a familia

255 eductase (WWOX) spans the second most common fragile site of the human genome, FRA16D, located at 16q

256 ed DNA sequences, such as those found in the fragile sites of chromosomes.

257 atase gene on 6p25.3 and adjoining the FRA7H fragile site on 7q32.3 in a systemic ALK-negative ALCL.

258 involved in preventing aphidicolin-sensitive fragile sites, our data suggest that the lesions respons

259 The distribution of common fragile sites parallels the positions of neoplasia-assoc

260 ctivate the ATR kinase in S phase and show a fragile-site phenotype in metaphase.

261 Common fragile sites predispose to specific chromosomal breakag

262 we investigated the AT islands in the FRA16B fragile site region for their possible roles in the orga

263 itical roles in maintaining the stability of fragile site regions.

264 occur either over tumour suppressors or over fragile sites, regions of increased genomic instability.

265 neous replication stress, however successful fragile site repair cannot be calculated using existing

266 f a site-specific double-strand break or DNA fragile site resulted in homologous recombination of rep

267 on drives the instability of a group of rare fragile sites (RFSs) characterized by CGG trinucleotide

268 d nuclear element 1s, suggesting that common fragile sites serve a function.

269 ffected genes overlap with early replicating fragile sites, show elevated levels of gammaH2AX, and su

270 that RECQL4-depleted human cells accumulate fragile sites, sister chromosome exchanges, and double s

271 checkpoint kinases, CHK1 and CHK2 on common fragile site stability in human cells.

272 Hus1 was found to be essential for fragile site stability, because spontaneous chromosomal

273 To further elucidate the pathways regulating fragile site stability, we have investigated the effects

274 omosome stability, and in particular, common fragile site stability.

275 but not ATM, is critical for maintenance of fragile site stability.

276 was previously shown that ATR is critical to fragile-site stability and that ATR-deficient cells have

277 ese data indicate that BRCA1 is important in fragile-site stability and that fragile sites are recogn

278 that this checkpoint function is involved in fragile-site stability.

279 mic loci/regions include centromeres, common fragile sites, subtelomeres, and telomeres.

280 d in cancer-associated genomic regions or in fragile sites, suggesting that miRNAs may play a more im

281 cation of a sequence element within a common fragile site that increases chromosome fragility.

282 long GAA/TTC tracts also act as chromosomal fragile sites that can trigger gross chromosomal rearran

283 Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearran

284 are possibly intrinsic properties of common fragile sites that may affect their replication and cond

285 on genomic regions, termed early replicating fragile sites, that may explain many AID-independent DSB

286 ation of fragile sites, a different class of fragile site, the 33-base pair AT-rich repeating DNAs de

287 nisms regulating the stability of chromosome fragile sites, therefore, has important implications in

288 rofile that is remarkably similar to that of fragile sites; these similarities are outlined and discu

289 been no direct evidence linking breakage at fragile sites to the formation of a cancer-specific tran

290 ven of 13 samples (85%) were deleted for the fragile site tumor suppressors WWOX and FHIT.

291 do not overlap known recessive oncogenes or fragile sites ("unexplained" homozygous deletions).

292 ormalities occurred preferentially at common fragile sites upon conditional Hus1 inactivation.

293 sult in chromosome breaks in regions termed "fragile sites." Using DNA microarrays, we mapped recombi

294 about the general characteristics of common fragile sites, we investigated the chromatin structure o

295 confer selective growth advantage, and over fragile sites, where they are thought to reflect an incr

296 Chromosomal fragile sites, which are regions of the genome that exhi

297 s in tumors are often associated with common fragile sites, which are specific genomic loci prone to

298 cannot progress through the A/T-rich FRA16B fragile site, while the regular replication mode is not

299 cture-forming ability, we refined legitimate fragile sites within the cytogenetically defined boundar

300 uences within the large nonexonic regions of fragile sites would be to identify conserved functional