ライフサイエンスコーパス: ORC

1 ORC sites in early and late replicating regions have sim

2 ORC, Cdc6 and Cdt1 act together to load hexameric MCM, t

3 ORC, Cdc6, and MCM are members of the AAA+ family of ATP

4 ORC, together with Cdc6 and Cdt1, mediate pre-replicativ

5 identified a urea-thiophene carboxamide, 1 (ORC-001), as protective against aminoglycoside antibioti

6 -subunit origin recognition complex (Orc1-6; ORC) recognizes the replication origin.

7 e present the optimization of 1 to yield 90 (ORC-13661).

8 nsequently the Cdt1-MCM2-7 complex activates ORC/Cdc6 ATP-hydrolysis to promote helicase loading.

9 Additionally, ORC is bound at many regions that do not undergo amplifi

10 We address ORC binding selectivity in vivo by mapping approximately

11 ic behavior creates a feedback loop allowing ORC/CDC-6 to repeatedly load MCM-2-7 and distribute lice

12 appropriate chromatin structure that allows ORC binding and subsequent origin firing.

13 Although ORC is conserved from yeast to humans, the DNA sequence

14 Although ORC-dependent loading of the replicative MCM helicase at

15 s the smallest and the least conserved among ORC subunits.

16 sisting of an ORC-Cdc6-Mcm2-7 complex and an ORC-Cdc6-Mcm2-7-Mcm2-7 complex are reported, which toget

17 We develop an ORC-based community identification algorithm based on th

18 o initiate DNA replication, or cells have an ORC-independent, CDC6-dependent mechanism to load MCM2-7

19 the 'initial' complex is transformed into an ORC/Cdc6/MCM2-7 (OCM) complex.

20 le human ORC(2-5) complex in the nucleus, an ORC(1-5) complex bound to chromatin, and an Orc6 protein

21 evidence for intermediates consisting of an ORC-Cdc6-Mcm2-7 complex and an ORC-Cdc6-Mcm2-7-Mcm2-7 co

22 atin loading was irreversible, but CDC-6 and ORC turned over rapidly, consistent with ORC/CDC-6 loadi

23 ributed substantially to origin activity and ORC binding.

24 Lrwd1 and ORC are known to co-purify with repressive histone marks

25 antly, the data suggest that nucleosomes and ORC have opposite preferences for DNA sequence and struc

26 gration were still observed between ONRC and ORC (p < 0.05).

27 lts support a model in which Orc6, Orc1, and ORC(2-5) are transported independently to the nucleus wh

28 eplication origins prior to Cdt1 release and ORC-Cdc6-Mcm2-7 complex formation, but how the second Mc

29 replication timing, early origin usage, and ORC binding.

30 f ORC hexamers, interfering with appropriate ORC functions.

31 g elements, both viral and cellular, such as ORCs, MCMs, and latency-associated nuclear antigen (LANA

32 via the same interaction that occurs between ORC and the C-terminal domains of the MCM helicases.

33 matches to this consensus than actually bind ORC or function as origins in vivo.

34 n absolute pH decline was observed with both ORC and ONRC after 1 hour.

35 r data support a model in which origin-bound ORC and Cdc6 recruit two Cdt1 molecules to initiate doub

36 Origin-bound ORC recruits Cdc6, and this ternary complex then promote

37 ntial for initiation of DNA replication, but ORC has non-essential functions outside of DNA replicati

38 ely compared to the standards established by ORC.

39 are disfavored by nucleosomes but favored by ORC.

40 been unclear how the origin DNA is guided by ORC-Cdc6 and inserted into the Mcm2-7 hexamer.

41 trical loading of individual MCM hexamers by ORC and directed MCM translocation into double hexamers

42 We show that helicase loading by ORC is inhibited by two distinct CDK-dependent mechanism

43 y of the pre-replication complex (pre-RC) by ORC-Cdc6 and Cdt1.

44 Here we show that MCM2-7 recruitment by ORC/Cdc6 is blocked by an autoinhibitory domain in the C

45 ence modulates DNA binding and remodeling by ORC, and that DNA bending promotes Mcm2-7 loading in vit

46 tats such as oxidized regenerated cellulose (ORC, TABOTAMP) and oxidized non-regenerated cellulose (O

47 A 3.9 angstrom structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed

48 The Saccharomyces cerevisiae ORC recognizes the ARS (autonomously replicating sequenc

49 tored in the Orbivirus Reference Collection (ORC) at IAH Pirbright, shows >99% nucleotide identity in

50 ned from the Orbivirus Reference Collection (ORC) at IAH, Pirbright, United Kingdom.

51 We show that origin recognition complex (ORC) and Cdc6 recruit multiple Cdt1 molecules to the ori

52 both subunits of origin recognition complex (ORC) and Cdc6, which are required to create a prereplica

53 suggest that the origin-recognition complex (ORC) and cell-division cycle 6 (Cdc6) proteins recognize

54 heterohexameric origin recognition complex (ORC) and functions as a replicative helicase.

55 presence of the origin recognition complex (ORC) and MCM proteins at these origins.

56 sphorylating the origin recognition complex (ORC) and promotes CMG formation by phosphorylating Sld2

57 y to recruit the origin recognition complex (ORC) and stimulate OriP replication.

58 alization of the origin recognition complex (ORC) and the minichromosome maintenance (MCM)2-7 complex

59 6, Cdt1, and the origin-recognition complex (ORC) assemble two heterohexameric Mcm2-7 complexes into

60 begins with the origin recognition complex (ORC) binding DNA sites called origins of replication.

61 The origin recognition complex (ORC) binds sites from which DNA replication is initiated

62 en a six-subunit origin recognition complex (ORC) binds to DNA.

63 The origin recognition complex (ORC) binds to the specific positions on chromosomes that

64 The origin recognition complex (ORC) defines origins of replication and also interacts w

65 e specificity in origin recognition complex (ORC) DNA binding complicates genome-scale chromatin immu

66 f binding of the origin recognition complex (ORC) in a differentiated metazoan tissue, we find that O

67 cruitment of the origin recognition complex (ORC) in a manner dependent on Suv4-20h and H4K20me3.

68 The origin recognition complex (ORC) is a DNA replication initiator protein also known t

69 The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase th

70 heterohexameric origin recognition complex (ORC) is essential for coordinating replication onset.

71 The Origin Recognition Complex (ORC) is essential for replication, heterochromatin forma

72 The Origin Recognition Complex (ORC) is necessary for orchestrating the initiation proce

73 ORC1, the Origin Recognition Complex (ORC) large subunit, is inherited into newly born cells a

74 replication, the origin recognition complex (ORC) loads two hexameric MCM helicases to form a head-to

75 d binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is hig

76 The origin recognition complex (ORC) of Saccharomyces cerevisiae binds origin DNA and co

77 x facilitated by Origin Recognition Complex (ORC) onto the chromatin during G1 phase of the cell cycl

78 The origin recognition complex (ORC) plays a key role during the initiation of DNA repli

79 Origin recognition complex (ORC) plays critical roles in the initiation of DNA repli

80 The origin recognition complex (ORC) specifies replication origin location.

81 CDKs) target two origin recognition complex (ORC) subunits, Orc2 and Orc6, to inhibit helicase loadin

82 y binding of the origin recognition complex (ORC) to DNA, but how ORC coordinates symmetrical MCM loa

83 NA1 recruits the origin recognition complex (ORC) to establish a replication origin at one element of

84 Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in t

85 Binding of the Origin Recognition Complex (ORC) to replication origins is essential for initiation

86 The six-subunit origin recognition complex (ORC), a DNA replication initiator, defines the localizat

87 on relies on the origin recognition complex (ORC), a DNA-binding ATPase that loads the Mcm2-7 replica

88 ion requires the origin recognition complex (ORC), a six-subunit assembly that promotes replisome for

89 alization of the origin recognition complex (ORC), and histone acetylation, yielding important insigh

90 and bound by the origin recognition complex (ORC), and subsequently activated by a cascade of events

91 eferences of the origin recognition complex (ORC), and the interference of transcription with the ass

92 re-RC) proteins: origin recognition complex (ORC), CDC-6, and CDT-1.

93 The origin recognition complex (ORC), Cdc6 and Cdt1 load Mcm2-7 into a double hexamer bo

94 Origin recognition complex (ORC), Cdc6, and Cdt1 assemble two MCM2-7 hexamers into o

95 each origin, the Origin Recognition Complex (ORC), Cdc6, and Cdt1 co-assemble to load the Mcm2-7 repl

96 Cs) requires the Origin Recognition Complex (ORC), Cdc6, and Cdt1.

97 he action of the origin recognition complex (ORC), Cdc6, Cdt1, and the Mcm2-7 complex.

98 e hexamer by the origin recognition complex (ORC), Cdt1 and Cdc6; the helicase is then activated by a

99 The origin recognition complex (ORC), composed of six subunits, ORC1-6, binds to origins

100 t subunit of the origin recognition complex (ORC), directly binds to septin complex and facilitates s

101 We identify the origin recognition complex (ORC), including LRWD1 as a subunit, to be a methylation-

102 re marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form

103 are bound by the origin recognition complex (ORC), which scaffolds assembly of a pre-replicative comp

104 taining protein, origin recognition complex (ORC)-associated (ORCA/LRWD1), plays a crucial role in st

105 cursors, and the origin recognition complex (ORC)-Cdc6-Cdt1-Mcm2-7 (OCCM) intermediate showed that ea

106 ns that bind the Origin Recognition Complex (ORC).

107 by a six-protein origin recognition complex (ORC).

108 teracts with the origin replication complex (ORC), a protein complex involved in both initiation of D

109 plex components (origin recognition complex [ORC] and minichromosome maintenance [MCM] complex).

110 proteins form origin recognition complexes (ORCs) that bind to replication origins during most of th

111 In this configuration, ORC is poised to direct the recruitment of the second he

112 lation of TRF2 is important for coordinating ORC binding with chromatin remodeling during the early S

113 ese selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels

114 we present a novel Ollivier-Ricci curvature (ORC) inspired approach to community identification in co

115 Open radical cystectomy (ORC) and pelvic lymph node dissection (PLND) is the stan

116 Histone H1 removal derepresses ORC and MCM chromatin binding, allowing efficient replic

117 DAFC-34B occurs in the absence of detectable ORC, although MCMs are present, suggesting a new amplifi

118 (cryo-EM) structures of DNA-bound Drosophila ORC with and without the co-loader Cdc6.

119 describe the crystal structure of Drosophila ORC at 3.5 A resolution, showing that the 270 kilodalton

120 ima facie, our data indicate that Drosophila ORC can switch between active and autoinhibited conforma

121 s loaded onto DNA as a single hexamer during ORC/Cdc6/Cdt1/MCM2-7 complex formation prior to MCM2-7 d

122 1 appears to act independently of the entire ORC, as other subunits of the complex, Orc4 and Orc5, ar

123 defined positions adjacent to the essential ORC-binding site within Saccharomyces cerevisiae origin

124 the ORC5.ORC3 interface that may facilitate ORC binding to DNA.

125 At first, ORC/Cdc6 recruits with the help of Cdt1 a single MCM2-7

126 st that Orc1 acts as a nucleating center for ORC assembly and then pre-replication complex assembly b

127 s highly dependent on the Orc1BAH domain for ORC association (orc1bahDelta-sensitive origins).

128 ow that the Orc1BAH domain was necessary for ORC's stable association with yeast chromosomes, and was

129 sential for nuclear localization but not for ORC assembly.

130 acterized domain of Orc3 and is required for ORC function and MCM2-7 loading in vivo.

131 g, positioning and assembling the functional ORC at the origins.

132 observed have not been described before: GFP-ORC-1 bound chromatin independently of ORC-2-5, and CDC-

133 for examining conserved mechanisms governing ORC's selection of origins within eukaryotic chromosomes

134 in recognition complex (ORC) to DNA, but how ORC coordinates symmetrical MCM loading is unclear.

135 in proteins in a variety of species, but how ORC functions in heterochromatin assembly remains unclea

136 l. use single-molecule imaging to reveal how ORC, Cdc6, and Cdt1 cooperate to load MCM2-7 onto DNA, e

137 maintain a nucleosome-free origin; however, ORC is required for the precise positioning of nucleosom

138 isolated proteins that interact with the HP1/ORC-associated protein (HOAP) capping protein, and ident

139 rt the structure of the active form of human ORC determined by X-ray crystallography and cryo-electro

140 Previous studies identified a soluble human ORC(2-5) complex in the nucleus, an ORC(1-5) complex bou

141 e report five cryoEM structures of the human ORC (HsORC) that illustrate the native flexibility of th

142 ulation of stochastic firing from identified ORC sites is in accord with replication timing data.

143 m2-7 release if components are missing or if ORC has been inactivated by cyclin-dependent kinase phos

144 gesting other chromosomal features influence ORC binding.

145 for the switch between active and inhibited ORC function at the G1-to-S-phase transition.

146 fined, only single roadblocks that inhibited ORC-DNA binding showed helicase loading defects.

147 a single MCM2-7 hexamer to form an 'initial' ORC/Cdc6/Cdt1/MCM2-7 complex.

148 only the OCM complex, but not the 'initial' ORC/Cdc6/Cdt1/MCM2-7 complex, is competent for MCM2-7 di

149 Instead, ORC binds nonspecifically to open (DNase I-hypersensitiv

150 nucleus where they can either assemble into ORC(1-6) or function individually.

151 der, impedes proper recruitment of Orc6 into ORC; biochemical studies reveal that this region of Orc6

152 ukaryote, appears to express an archaea-like ORC consisting of a single Orc1/Cdc6-like protein.

153 the presence of competitor DNA and limiting ORC concentrations, replication becomes origin-dependent

154 The helicase loaders ORC-Cdc6 function to recruit a single Cdt1-Mcm2-7 heptam

155 In contrast, dynamic domains exhibited low ORC densities in both cell types, suggesting that origin

156 Using high-throughput sequencing to map ORC binding and nucleosome positioning, we show that yea

157 l overlap between budding yeast and metazoan ORC has been unclear.

158 6 is a DNA-binding subunit of human/metazoan ORC and may play roles in targeting, positioning and ass

159 atin must play an important role in metazoan ORC's ability to recognize origins, it is unclear whethe

160 ermined the subunit organization of metazoan ORC, revealing that it adopts a global architecture very

161 In particular, metazoan ORC shows no obvious DNA sequence specificity, whereas y

162 In metazoans, ORC associates with origin DNA during G1 and with hetero

163 e similar properties, but there are far more ORC sites in early replicating regions.

164 We show that, in human cells, multiple ORC subunits associate with hetereochromatin protein 1 (

165 y number restored, neither transcription nor ORC binding is reinstated.

166 ntigen (PCNA), and polymerase delta, but not ORC and MCM proteins.

167 onto DNA requires the combined activities of ORC, Cdc6, and Cdt1.

168 s with and stimulates the ATPase activity of ORC-Cdc6.

169 Genome-wide analyses of ORC binding in ORC1 and orc1bahDelta cells revealed that

170 G1/S boundary, Orc3 facilitates assembly of ORC/HP1 proteins to chromatin.

171 results suggest ORCA-mediated association of ORC to chromatin is critical to initiate preRC assembly

172 h ORC and modulates chromatin association of ORC.

173 However, what regulates the binding of ORC to chromatin is not understood.

174 lation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acet

175 Here we show that ORC1--a component of ORC (origin of replication complex), which mediates pre-

176 tor, TbORC1B, is not a static constituent of ORC but displays S-phase restricted nuclear localization

177 r cell cycle and/or developmental control of ORC functions.

178 destruction, with subsequent dissociation of ORC from chromosomes.

179 se loading is accompanied by dissociation of ORC, Cdc6, and Cdt1 from origin DNA.

180 ction site, which promotes the engagement of ORC at the N-terminal homodimerization interface of MCM.

181 me mutations in Orc6 impair the formation of ORC hexamers, interfering with appropriate ORC functions

182 alpha-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA int

183 on an intact WD40 domain but independent of ORC proteins.

184 mes recruit MCM2-7 to origins independent of ORC.

185 , and CDC-6 bound chromatin independently of ORC, whereas CDT-1 and MCM-2-7 DNA binding was interdepe

186 : GFP-ORC-1 bound chromatin independently of ORC-2-5, and CDC-6 bound chromatin independently of ORC,

187 on of helicase loading without inhibition of ORC-DNA binding only when roadblocks were placed on both

188 and embryonic stem cells results in loss of ORC association to chromatin, concomitant reduction of M

189 molecule of ORCA can bind to one molecule of ORC, one molecule of Cdt1, and two molecules of geminin.

190 Large genomic regions with a paucity of ORC sites are strongly associated with common fragile si

191 ing helicase loading, CDK phosphorylation of ORC causes a twofold reduction of initial Cdt1/Mcm2-7 re

192 mportantly, CDK-dependent phosphorylation of ORC inhibits OCM establishment to ensure once per cell c

193 n the evolution of the binding properties of ORC in S. pombe and other eukaryotic species to target p

194 nding affinity and functional recruitment of ORC.

195 lify, a consequence of distant repression of ORC binding and origin activation.

196 r results demonstrate that specific sites of ORC and MCM enrichment can be detected within a mammalia

197 initiation activity surrounding the sites of ORC and MCM enrichment.

198 Finally, a structure of ORC was determined with endogenous DNA bound in the core

199 udies indicate that multiple subcomplexes of ORC exist at heterochromatin, with Orc1 stably associati

200 s, the level of Orc1, the largest subunit of ORC, is regulated during the cell division cycle, and th

201 The largest subunit of ORC, Orc1, is particularly interesting because it contai

202 In contrast, one ORC molecule directs loading of both helicases in each d

203 , an ancient unicellular eukaryote, only one ORC-related initiator, TbORC1/CDC6, has been identified

204 on OCCM," the main body of Mcm2-7 docks onto ORC-Cdc6, and the origin DNA is bent and positioned adja

205 hed OCCM," the Mcm3 and Mcm7 WHDs latch onto ORC-Cdc6 while the main body of the Mcm2-7 hexamer is no

206 t and pinch motions were observed in an open ORC conformation revealing a hinge at the ORC5.ORC3 inte

207 It colocalized GABA and MIP but not AT or ORC immunoreactivity.

208 epeat domain-containing protein 1 (LRWD1) or ORC-associated (ORCA) in human cells that interacts with

209 ecule pull-down assays demonstrate that ORCA-ORC (Origin Recognition Complex) and multiple H3K9 KMTs

210 oinhibitory peptides (MIPs), and orcokinins (ORCs) were part of both entrainment pathways, whereas al

211 pairs ORC1 occupancy at replication origins, ORC chromatin loading and cell-cycle progression.

212 otein that binds weakly, if at all, to other ORC subunits.

213 h heterochromatin in G1 phase, whereas other ORC subunits have transient interactions throughout the

214 t proteins that did not co-purify with other ORC subunits.

215 During S phase, ORC and CDC-6 were excluded from nuclei, and DNA was ove

216 rotein occupancy profiles resolved a precise ORC-dependent footprint at 269 origins in G2.

217 ture of yeast origin architecture to promote ORC binding and origin activity, and helps explain why a

218 ding yeast, the eukaryotic initiator protein ORC (origin recognition complex) binds to a bipartite se

219 BNA1's DNA-binding domain is able to recruit ORC to DS, but either this step or subsequent replicatio

220 ion status plays a direct role in recruiting ORC through the binding properties of ORC1 and ORCA/LRWD

221 e demonstrate that ORCA efficiently recruits ORC to chromatin.

222 MCM-2-7 chromatin loading further reduced ORC and CDC-6 DNA binding.

223 involved in helicase loading or in releasing ORC from loaded MCM2-7.

224 This reaction requires ORC and Cdc6 ATPase activity, but it is unknown how thes

225 e hexamer at origins in a reaction requiring ORC, Cdc6, and Cdt1, also called pre-replicative complex

226 rings are loaded independently via the same ORC-mediated mechanism, at two inverted DNA sites(4,5).

227 re defined at the level of origin selection (ORC binding) and likely mediated by chromatin accessibil

228 Significantly, ORC is bound across domains spanning 10 or more kilobase

229 n interactions exist between four of the six ORC subunits, unanticipated features are also evident.

230 mans, the DNA sequence elements that specify ORC binding are not.

231 at being an NDR is not sufficient to specify ORC binding.

232 contribute in an additive manner to specify ORC-binding sites.

233 C-associated protein (ORCA/LRWD1) stabilizes ORC on chromatin.

234 /LRWD1), plays a crucial role in stabilizing ORC to chromatin.

235 occupancy only in G1, suggesting that stable ORC chromatin association in G2 is a determinant of orig

236 Here we show that stable ORC(1-6) complexes also can be purified from human cell

237 Here, we have mapped sites of biotin-tagged ORC and MCM protein binding in G1-synchronized populatio

238 We find that ORC and ONRC inhibit fibroblast proliferation, migration

239 differentiated metazoan tissue, we find that ORC binding is dramatically reduced within these large d

240 We find that ORC, Cdc6, and Cdt1 contain intrinsically disordered reg

241 The results indicate that ORC binding sites and other essential origin sequences a

242 Comparative analyses indicate that ORC encircles DNA, using its winged-helix domain face to

243 itioning information in silico revealed that ORC and MCM map to regions of low measured and predicted

244 Here we show that ORC and Cdc6 mutants defective in ATP hydrolysis are com

245 We show that ORC can locate and stably bind origins within large trac

246 ng a chemical biology approach, we show that ORC-Cdc6-Cdt1-dependent helicase loading occurs through

247 This work shows that ORC architecture and regulation are diverged features of

248 binding to heterochromatin, suggesting that ORC and HP1 proteins are mutually required for each othe

249 cific transcription factors, suggesting that ORC is not bound or recruited to specific DNA sequences.

250 action at satellite repeats, suggesting that ORC together with HP1 proteins may be involved in organi

251 The ORC binding profile is broader than those of sequence-sp

252 The ORC-associated protein (ORCA/LRWD1) stabilizes ORC on ch

253 The ORC-based algorithm is able to identify communities with

254 of the cell-cycle, Cdc6 binds to ORC and the ORC-Cdc6 complex loads in a multistep reaction and, with

255 yotic replication origins are defined by the ORC-dependent loading of the Mcm2-7 helicase complex ont

256 Thus, either the ORC ring lacking a subunit, even its ATPase subunit, can

257 unity identification methods, we examine the ORC-based algorithm with stochastic block model artifici

258 nstitute the primary DNA binding site in the ORC ring and cooperate with the winged-helix domains to

259 edicted to affect ATP binding, influence the ORC-Cdc6 interaction and MCM2-7 recruitment.

260 hat likely impact DNA incorporation into the ORC core.

261 A key intermediate is the ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) complex in which DNA has bee

262 in, Orc1b, as an additional component of the ORC and showed that both Orc1b and Orc1/Cdc6 associate w

263 lpha-satellite sequences for proteins of the ORC complex, suggesting that CENP-B may have a role in r

264 the intrinsic geometric underpinning of the ORC offers a natural approach to discover inherent commu

265 We further show that the dynamics of the ORC-Cdc6 interaction dictate Mcm2-7 loading specificity

266 ATP-hydrolysis promotes the formation of the ORC/Cdc6/MCM2-7 (OCM) complex, which functions in MCM2-7

267 and helps explain why a strong match to the ORC binding site is insufficient to identify origins wit

268 ggested a sequential mechanism, in which the ORC-dependent loading of the first hexamer drives the re

269 active helicase complex, associate with the ORC, and regulate DNA replication remains unknown.

270 ted during the cell division cycle, and thus ORC is a dynamic complex.

271 DNA, allosterically coupling DNA binding to ORC's ATPase site.

272 In addition to binding to ORC, ORCA associates with Cdt1 and its inhibitor, gemini

273 ate M-phase of the cell-cycle, Cdc6 binds to ORC and the ORC-Cdc6 complex loads in a multistep reacti

274 al recruitment of the Cdt1/Mcm2-7 complex to ORC.

275 ealed that the Orc1BAH domain contributed to ORC's association with most yeast origins, including a c

276 s into how the Orc1BAH domain contributes to ORC's selection of replication origins, as well as new t

277 n E/Cdk2 activity were strictly localized to ORC binding sites.

278 with sufficient follow-up to compare MIRC to ORC for the treatment of invasive BCa before the oncolog

279 that replication timing is due primarily to ORC density and stochastic firing of origins.

280 there is a vast excess of Mcm2-7 relative to ORC assembled onto chromatin in G1.

281 fficient MCM loading requires binding of two ORC molecules to two ORC binding sites.

282 requires binding of two ORC molecules to two ORC binding sites.

283 e complex provides a basis for understanding ORC activity as well as molecular defects observed in Me

284 CM open for DNA entry and bound to ATP until ORC-Cdc6 triggers ATP hydrolysis by MCM, promoting both

285 itional origin sequence known to be a weaker ORC-DNA-binding site.

286 ilar among developmental stages during which ORC is or is not bound, indicating that being an NDR is

287 ORCA colocalizes with ORC and shows similar cell-cycle dynamics.

288 trongly inhibited by ONRC when compared with ORC (p < 0.05).

289 with locally advanced disease compared with ORC series.

290 ng were observed for ONRC when compared with ORC.

291 and ORC turned over rapidly, consistent with ORC/CDC-6 loading multiple MCM-2-7 complexes.

292 ed (ORCA) in human cells that interacts with ORC and modulates chromatin association of ORC.

293 to the MCM2-7 double-hexamer, interacts with ORC/Cdc6 and is salt-sensitive, classifying the arrested

294 omplexes exhibit little co-localization with ORC or replication foci and can function as dormant orig

295 ivated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins.

296 atch the lower pH values typically seen with ORC and ONRC, significant differences in cell proliferat

297 sts grown in collagen-gels were treated with ORC or ONRC, and ECM contraction was measured utilizing

298 al fibroblasts were inoculated in vitro with ORC and ONRC.

299 lear whether chromatin plays a role in yeast ORC's recognition of origins.

300 ious DNA sequence specificity, whereas yeast ORC binds to a specific DNA sequence within all yeast or