ライフサイエンスコーパス: myc gene

1 es within approximately 1,400 bp 5' to the c-myc gene.

2 with the promoter region of the endogenous c-myc gene.

3 ld greater than that of a known MAR in the c-myc gene.

4 ress the transcriptional elongation of the c-myc gene.

5 stoma gene product and upregulation of the c-myc gene.

6 activating expression of the translocated c-myc gene.

7 ssed in cells carrying extra copies of the N-myc gene.

8 ar upstream element (FUSE) upstream of the c-myc gene.

9 imidine sequence in the P2 promoter of the c-myc gene.

10 rich strand from the promoter of the human c-MYC gene.

11 r more sites within 2.4 kb upstream of the c-myc gene.

12 t in the transcriptional activation of the c-MYC gene.

13 ion at the first exon/intron border of the c-myc gene.

14 es induced by the top2(S740W) in the human c-myc gene.

15 o restriction fragments from the germ-line c-myc gene.

16 s the expression pattern of the endogenous N-myc gene.

17 gain of chromosome 15, which contains the c-myc gene.

18 s a transcriptional repressor of the human c-myc gene.

19 ngle strand of DNA in the 5' region of the c-myc gene.

20 n factors for optimal transcription of the c-Myc gene.

21 druplex formation within the intron of the N-myc gene.

22 t," a few hundred kilobases telomeric to the Myc gene.

23 erences in expression or function of a given MYC gene.

24 ivity at the Ig switch region and off-target Myc gene.

25 was not dependent upon transcription of the Myc gene.

26 ls even as cells show amplification of the N-myc gene.

27 tic increase in ERalpha recruitment to the c-Myc gene.

28 ed at promoter-proximal pause sites of the c-myc gene.

29 pproximately 820-bp promoter region of the c-myc gene.

30 ssion, including expression of the socs3 and myc genes.

31 ls with chromosomally integrated amplified N-myc genes.

32 naturally metastatic cells with amplified N-myc genes.

33 liferation via repression of cyclin D1 and c-myc genes.

34 stage-specific activation of translocated c-myc genes.

35 ivating the transcription of cyclin D1 and c-Myc genes.

36 e and in the promoter regions of bcl-2 and c-myc genes.

37 aled common insertions in either notch1 or c-myc genes.

38 uroblastoma selects for cells that amplify N-myc genes.

39 e E-responsive promoter regions of pS2 and c-myc genes.

40 nRNP) K is a transcription factor for the c- myc gene, a proto-oncogene critical for the regulation o

41 tal translocation region by insertion of a c-myc gene about 50 kb from the IgH intron enhancer in a y

42 Herein, aspects of c-myc gene activation and the function of the c-Myc protei

43 Mutation of the cell cycle regulator N-myc gene also leads to an apparently identical phenotype

44 ble antibodies have facilitated the study of MYC gene alterations and protein expression in large ser

45 MYC gene alterations have been identified in other matur

46 MYC gene alterations in large B-cell lymphomas are frequ

47 ed Myc expression in cancers can result from MYC gene amplification and translocation but also from a

48 Although MYC gene amplification and translocations have been obse

49 The data implicate L-MYC gene amplification and/or overexpression in human Ov

50 myc gene amplification has been identified in many large

51 may be a better prognostic indicator than N-myc gene amplification in neuroblastoma.

52 equently in human B lymphoid tumors, while N-myc gene amplification is frequent in human neuroblastom

53 expression of c-Myc mRNA, caused either by c-myc gene amplification or by enhanced signaling via STAT

54 Among 11 SCLC cell lines with L-myc gene amplification, four were found to have alterati

55 he XRCC4/p53-deficient MBs have high-level N-myc gene amplification, often intrachromosomally in the

56 to induce transcription of the endogenous c-myc gene and cell entry into S phase.

57 structural characterization of the chicken c-myc gene and have begun to investigate c-myc transcripti

58 regulate the expression of the endogenous c-myc gene and is a potent activator of the c-myc promoter

59 outlines the nature and regulation of the c-myc gene and of c-Myc and presents the systems and condi

60 e chromosomal translocations involving the c-myc gene and one of the Ig loci.

61 rks diverge from an origin 5' to the human c-myc gene and that a 2.4-kb core fragment of the origin d

62 lex that binds to the MIF-1 element in the c-myc gene and the major histocompatibility complex class

63 Focal CNAs affecting the MYC gene and the PTEN gene were observed only in a minor

64 und to co-localize at the promoters of the c-myc gene and the RPPH1 sRNA in vivo.

65 phoma (BL) cell lines carry a translocated c-myc gene and, in 60-80% of cases, exhibit mutations in t

66 e a transcriptional block on the Cox-2 and c-myc genes and that this block may be a potential target

67 region of the progesterone-regulated avian c-myc gene, and nuclear matrix-like attachment sites flank

68 g defects, lower levels of REF1/Aly at the c-myc gene, and nuclear retention of bulk HeLa poly(A)+ RN

69 chromosome 8q24), the map location of the c-Myc gene, and six of the tumors exhibited copy number lo

70 ains after proviral integration within the c-myc gene, and subsequent expansion of Myc-overexpressing

71 kens after proviral integration within the c-Myc gene, and subsequent expansion of Myc-overexpressing

72 Deletion mutations were introduced into myc genes, and the levels of their mRNAs were compared w

73 the regulation or expression level of the c-myc gene are among the most common found in human and an

74 locations of the coding exons of the human c-myc gene are consistent features of human Burkitt lympho

75 ic morphology and overexpress the cellular c-MYC gene are highly aggressive and carry a very poor pro

76 h the physically linked cad and endogenous N-myc genes are coamplified.

77 The HER2 (ERBB2) and MYC genes are commonly amplified in breast cancer, yet l

78 lyses revealed that both the mouse and human Myc genes are direct transcriptional targets of N1(IC) a

79 nd tamoxifen at ER alpha-regulated pS2 and c-myc genes are in part mediated by HER-2/neu.

80 ocations juxtaposing immunoglobulin (Ig) and MYC genes are the hallmarks of human Burkitt lymphoma (B

81 The MYC genes are the most frequently activated oncogenes in

82 Although the structure and expression of Myc genes are well characterized, the function and bioch

83 f RNA transcripts detected fusion of the HPV/Myc genes, arising from apparent microhomologous recombi

84 ulation of B-cell survival and confirm the c-myc gene as one of the downstream targets of A-myb in th

85 d levels of acetylated histone H3 within the MYC gene associated with reduced levels of MYC protein a

86 elial regression through the repression of c-myc gene at the chromatin level.

87 The precise mechanism of myc gene autoregulation is unknown.

88 t lymphomas (BL) and murine plasmacytomas, c-myc genes become juxtaposed to immunoglobulin heavy-chai

89 The c-myc gene becomes transcriptionally activated as a conseq

90 , located in the 5'-flanking region of the c-myc gene, between nucleotides -1406 and -1387 (relative

91 HPV-16 genome was integrated adjacent to the Myc gene, both of which were amplified 40-fold.

92 hancers (WREs) located in close proximity to MYC gene boundaries.

93 a cell lines that do not have an amplified c-myc gene but differ in their p53 status, high c-myc leve

94 contrast, lack structural alterations in the MYC gene, but have deregulated Myc protein due to the ac

95 prostate tumors have amplifications of the c-Myc gene, but the precise role of c-Myc in prostate canc

96 id gene itself as well as in the bcl-6 and c-myc genes, but not in the p53 gene, consistent with aber

97 s the MYC promoter and thereby activates the MYC gene by a beta-catenin/transcription factor 4 (TCF4)

98 is insertional activation of the cellular N-myc gene by integrated viral DNA.

99 sible mechanism for transactivation of the c-myc gene by mutant p53 is proposed.

100 ng c-Myc activity due to disruption of the c-myc gene by targeted homologous recombination are defect

101 involves direct promoter targeting of the c-myc gene by the complexes.

102 tt lymphoma, because avian retroviruses with myc genes cause cancer in birds.

103 It is well established that Ha-ras and c-myc genes collaborate in promoting transformation, tumor

104 s downregulate expression of the amplified N-myc gene, concurrent with the arrest of cell proliferati

105 All v-myc genes contain point mutations which seem to confer a

106 Moreover, inappropriate expression of c-myc genes contributes to the development of many types o

107 o BL develop in mice bearing a mutated human MYC gene controlled by a reconstructed Ig lambda locus e

108 FDG signature was similarly associated with MYC gene copy gain, increased MYC transcript levels, and

109 ate that modulating HuD expression affects N-myc gene copy number as well as expression.

110 Thus, N-myc gene copy number is modulated by alteration of HuD e

111 N-myc gene copy numbers and transcription rates are simila

112 a frequently lethal childhood tumor in which MYC gene deregulation, commonly as MYCN amplification, p

113 f the chromosomal translocation leading to c-myc gene deregulation, remains unclear.

114 Here we show that the Drosophila Myc gene diminutive is an X-linked numerator.

115 , we showed that T3 directly activated the c-Myc gene during metamorphosis in the intestine via bindi

116 ers in either orientation, 5" and 3", of the myc gene elevated reporter activity from 2- to 160-fold,

117 cruitment of androgen receptor (AR) to the c-Myc gene enhancer and induced H3K9 demethylation, increa

118 1,25D inhibited MYC gene expression and accelerated its protein turnover

119 neuroendocrine differentiation, increased L-myc gene expression and decreased c-myc gene expression.

120 er, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation.

121 1 treatment of B cell lymphomas decreases c-myc gene expression and induces apoptosis.

122 iption, mediated by a rapid suppression of c-myc gene expression and its binding to KOR promoters, an

123 Aberrant MYC gene expression by the Wnt/beta-catenin pathway is i

124 Both anaplasia and increased c-myc gene expression have been shown to be negative progn

125 nts (95%), DNA index (ploidy) in 18 (90%), N-myc gene expression in 14 (70%), and cytogenetic analysi

126 trate that the suppressive effect of OM on c-myc gene expression in H3922 cells occurs at the transcr

127 y of TFOs designed to act as repressors of c-myc gene expression in human leukemia and lymphoma cells

128 mily, we determined the normal patterns of L-myc gene expression in the developing mouse by RNA in si

129 Aberrant myc gene expression in transgenic mice is correlated wit

130 Deregulated c-myc gene expression is associated with many human and an

131 C-myc gene expression is greater in the undamaged carotid

132 Therefore, post-transcriptional control of N-myc gene expression must differ between these cell types

133 conclude that RA-mediated up-regulation of L-myc gene expression occurs through stimulation of transc

134 which alters immunoglobulin mu (Igmu) and c-myc gene expression, RTA did not affect Igmu and c-myc e

135 ons in endothelin-induced c-fos, c-jun, or c-myc gene expression, suggesting either that the inhibito

136 virus is associated with the activation of N-myc gene expression, usually by viral DNA integration in

137 ivity and the effect of these compounds on c-MYC gene expression, we have demonstrated, using a cellu

138 estigate mechanisms of regulation of human N-myc gene expression, we observed that N-myc promoter-chl

139 ene, mediated by a rapid downregulation of c-myc gene expression.

140 etylcholinesterase activity, and decreased N-myc gene expression.

141 e to bind to NF-kappaB elements and induce c-myc gene expression.

142 pression of beta-interferon (IFN-beta) and c-myc gene expression.

143 ited IGF-I-dependent changes of GAP-43 and c-myc gene expression.

144 he H4R3me2a mark, and the complex promotes c-MYC gene expression.

145 on is not a major factor in the control of L-myc gene expression.

146 reased L-myc gene expression and decreased c-myc gene expression.

147 tional and post-transcriptional control of L-myc gene expression.

148 Es accompanies transcriptional activation of MYC gene expression.

149 MYC also elevated let-7a miRNA and decreased Myc gene expression.

150 Tbx20 led to increased Tbx2 and decreased N-myc gene expression.

151 s multiple biosynthetic routes and induces c-MYC gene expression.

152 alterations affecting proto-oncogenes of the myc gene family are frequently detected in human lung ca

153 e basis for the evolutionary conservation of myc gene family has remained unclear.

154 Therefore, the myc gene family must have evolved, to a large extent, to

155 h DNA oligonucleotide originating from the N-myc gene folds into G-quadruplex structures in the prese

156 The targeted knockout of the c-myc gene from rat fibroblasts leads to a stable defect i

157 in 73% of animals, either the c-myc or the N-myc genes had been disrupted and deregulated.

158 The c-myc gene has been implicated in multiple cellular proces

159 region of mutant p53 responsiveness in the c-myc gene has been mapped to the 3' end of exon 1; (iii)

160 gged with an immunoreactive epitope from the myc gene has been used to map the position of the glycos

161 n certain types of Burkitt's lymphoma, the c-myc gene has undergone translocation to the S regions as

162 MYC genes have both essential roles during normal develo

163 berrations (e.g., translocations) in a given MYC gene in a particular tumor progenitor cell type.

164 le in the deregulation of the translocated c-myc gene in Burkitt's lymphoma and suggest that interfer

165 The deregulation of expression of the c-myc gene in Burkitt's lymphoma results from the transloc

166 f the frequent mutations that occur in the c-myc gene in Burkitt's lymphomas.

167 gest aberrant translational control of the c-myc gene in cell lines derived from patients with MM, wh

168 The origin of replication of the c-myc gene in HeLa cells was previously identified at low

169 cancer drugs within a 683-bp region of the c-myc gene in human CEM leukemia cells.

170 rther reinforces the important role of the c-Myc gene in KSHV lytic replication and latency.

171 e differentiation program shutting off the c-Myc gene in large pre-B cells.

172 , we demonstrated an essential role of the c-myc gene in promoting cell survival of WEHI 231 cells in

173 the promoter and downstream regions of the c-myc gene in response to estrogen.

174 he transfected promoter and the endogenous N-myc gene in single-copy, but not amplified lines.

175 ks, which moved through this region of the c-myc gene in the 5' to 3' direction, were specifically ar

176 tiation of DNA replication upstream of the c-MYC gene in the HeLa cell cycle.

177 Enhanced expression of the amplified N-myc gene in the tumor cells may be associated with poor

178 the PNNs and tumors, and amplification of C-MYC gene in the tumors were confirmed by Southern blot a

179 uence (CCCTCCCCA; CT-element) of the human c-myc gene in vitro.

180 ta-cat promotes H3K4 trimethylation at the c-Myc gene in vivo.

181 site was detected in the first exon of the c-myc gene in VM-26-treated cells.

182 Deletion of both c-Myc genes in B cells led to severely impaired proliferat

183 attern of deregulated expression of linked c-myc genes in BL and plasmacytoma cell lines.

184 crease in histone acetylation along linked c-myc genes in Raji BL cells.

185 eview evidence implicating each of the above MYC genes in specific neoplastic diseases and have attem

186 melting of specific cis elements of active c-myc genes in vivo suggested that transcriptionally assoc

187 t the activity of a cellular oncogene, the c-MYC gene, in addition to inactivation of the tumor suppr

188 mal human fibroblasts with one copy of the c-myc gene inactivated by targeted homologous recombinatio

189 fine numerous biological activities of the c-myc gene, including transformation, immortalization, blo

190 Ba/F3 cell proliferation, suggesting that c-Myc gene induction is required for IFN-gamma-mediated ce

191 bursal lymphoma in chickens after proviral c-myc gene integration, while the HB-1 retrovirus carries

192 By inserting an intact mouse Myc gene into the mouse genome, proximal to the Ig enhan

193 target gene of c-Myb and activation of the c-myc gene is a necessary event in Myb-mediated transforma

194 Amplification of the N-myc gene is a significant adverse prognostic factor in n

195 ar run-on analyses, we determined that the N-myc gene is actively transcribed in all cell types exami

196 not clear if activation of the endogenous c-myc gene is an apoptotic signal after toxicant exposure.

197 sporadic TNBC patients, amplification of the MYC gene is correlated with increased expression of the

198 differential functional expression of the c-myc gene is discussed.

199 The c-myc gene is frequently deregulated and overexpressed in

200 Expression of the c-myc gene is frequently dysregulated in malignant tumors

201 Transgenic mice in which the myc gene is juxtaposed to an immunoglobulin enhancer (E(

202 The N-myc gene is overexpressed due to genomic amplification i

203 Although the c-myc gene is overexpressed in approximately 70% of human

204 hermore, we and others have shown that the c-myc gene is potently transactivated by A-Myb in several

205 Transcription of the c-myc gene is repressed by Blimp-1 during B-cell different

206 tion that the deregulated expression of each MYC gene is reproducibly associated with only certain na

207 The expression of the Myc gene is synergistically regulated by KLF1 and KLF2,

208 sequence and expression of the endogenous c-myc gene is the same in resistant and susceptible birds,

209 The c-myc gene is translocated to one of the immunoglobulin ge

210 ression, transforming function of retroviral myc genes is restricted to avian cells, and that of retr

211 The MYCC (c-MYC) gene is amplified in 30-60% of human ovarian cancer

212 binding site, conserved in mouse and human c-myc genes, is found immediately downstream of the major

213 ion including feedback autoregulation of the MYC gene itself.

214 Furthermore, c-myc gene knockout fibroblasts are refractory to transfor

215 A cis element of the human c-myc gene, known to be melted in vivo, and its associated

216 smid containing the promoter region of the c-myc gene linked to a reporter gene.

217 methodology, we have established that the c-myc gene, located at 8q21, exhibited amplification of 87

218 serting a single-copy histidine-tagged mouse Myc gene, Myc(His), into the mouse Ig heavy-chain Calpha

219 The human N-myc gene normally is expressed in only a subset of fetal

220 The prototypic v-Myc gene of MC29 virus differs from avian c-Myc by a ser

221 HN2, and only detectable in the amplified c-myc gene of the Colo320HSR cell line.

222 slinks were not detectable in the N-ras or c-myc genes of LS174T, J6 or U937 cells treated with HN2,

223 suggesting that the amplification for the c-myc gene on 8q was relatively specific, and this was con

224 g array of biological activities makes the c-myc gene one of the most intriguing oncogenes and presen

225 r in tumors harboring either the wild-type c-Myc gene or the NCR allele.

226 show that a single extra copy of either the Myc gene or the region encompassing Pvt1, Ccdc26 and Gsd

227 e stably transfected C2C12 cells with mutant myc genes or chimeric genes in which various myc sequenc

228 The transcriptional effects of deregulated myc gene overexpression are implicated in tumorigenesis

229 is was identified as an early consequence of myc gene overexpression in two models of retroviral lymp

230 s may block Myc function by repressing the c-myc gene P2 promoter, as well as by antagonizing Myc-dep

231 These data indicate that c-Myc gene plays an important role in mediating CD437-indu

232 le-stranded far upstream element of active c-myc genes, possesses potent transcription activation and

233 Segments of the human c-myc gene possessing non-B structure in vivo located with

234 v-abl and frequently harbored a rearranged c-myc gene, probably as a result of chromosome translocati

235 The c-myc gene produces an oncogenic transcription factor that

236 tone deacetylase 1 and 2 to the endogenous c-myc gene promoter and the subsequent deacetylation of it

237 n can bind to the cis-element of the human c-myc gene promoter and to the gene promoter of STZ/ZAT10,

238 ulates the transcriptional activity of the c-myc gene promoter by dissociating the active form of NF-

239 Both TIP30 and CIA are recruited to the c-myc gene promoter by liganded ERalpha in the second tran

240 ith high affinity a specific region at the c-MYC gene promoter characterized by parallel G-quadruplex

241 binding site (acceptor site) for PR in the c-myc gene promoter is composed of RBF dimers bound to a s

242 he TDRD3-TOP3B complex is recruited to the c-MYC gene promoter primarily by the H4R3me2a mark, and th

243 the expression of c-myc by binding to the c-myc gene promoter.

244 ssociated region (MAR) of the Pg-regulated c-myc gene promoter.

245 ubtype of Notch-independent T-ALLs that bear Myc gene rearrangements and Pten mutations.

246 ted Burkitt or Burkitt-like morphology and c-myc gene rearrangements and, therefore, appeared to be B

247 BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated

248 onstrated in 3 other cases (19%), although c-myc gene rearrangements were not seen by Southern blotti

249 lymphoma, and all 12 cases studied lacked c-myc gene rearrangements.

250 gets of AFF4/SEC, and SEC recruitment to the MYC gene regulates its expression in different cancer ce

251 ver half a megabase of DNA upstream of their Myc gene removed still thrive in the absence of stress.

252 ing to the specific promoter region of the c-Myc gene, resulting in drastic suppression of c-Myc expr

253 In mice, complete disruption of the N-myc gene results in fetal death on the first day of rena

254 hose whose tumors had amplification of the N-myc gene (RR = 0.26; P = .112; EFS, 67% v 0%).

255 The c-myc gene's regulatory sequences were normal in those cel

256 g that dispersion and amplification of the c-MYC gene sequences occurred after and was most likely tr

257 ly patients whose tumors have an amplified c-myc gene show improved disease-free and overall survival

258 The c- and N- myc genes showed three general classes of sequence conse

259 ry closely related to the structure of the c-myc gene single-strand binding proteins (MSSPs).

260 tes in the promoters of both the c-myb and c-myc genes, suggesting that c-myb and c-myc may be among

261 However, the complexity and diversity of Myc gene targets has confounded attempts at identifying

262 kilobase pair region upstream of the human c-myc gene that contains 86 CpGs.

263 L-3 and IFN-gamma induce expression of the c-Myc gene that is not dependent on the Stat1 activity.

264 atopoietic tumor cell lines having altered c-myc genes, the c-Myc S proteins are constitutively expre

265 imidine-rich DNA sequence upstream of the c -myc gene to activate its expression.

266 a is characterized by translocation of the c-MYC gene to an immunoglobulin enhancer region, resulting

267 diester TFOs directed to four sites in the c-myc gene to inhibit gene expression and proliferation of

268 cting homopyrimidine tract upstream of the c-myc gene to which the well-characterized transcription f

269 novel cAMP-dependent increase in renin and c-myc gene transcription by binding as a monomer to a uniq

270 monstrate the rapid and potent abrogation of MYC gene transcription by representative small molecule

271 ibitor p27 which was an indirect effect of c-myc gene transcription control by Ada3.

272 ium nitroprusside (SNP), rapidly represses c-myc gene transcription in a protein synthesis-independen

273 paB and AhR resulting in the activation of c-myc gene transcription in breast cancer cells.

274 ed as a DNA-binding protein that regulates c-Myc gene transcription through binding to the far upstre

275 ctor activity, which regulates the rate of c-myc gene transcription, to determine whether the increas

276 ced histone H3 acetylation and activation of MYC gene transcription.

277 s a cAMP-responsive regulator of renin and c-myc gene transcriptions by the interaction with a specif

278 er transplantation of human NSCs cloned by v-myc gene transfer, HB1.F3 cells, is a feasible therapeut

279 s transcribed from two similarly constructed myc genes transiently cotransfected into proliferating C

280 se results implicate H-DNA-induced DSBs in c-myc gene translocations in diseases such as Burkitt's ly

281 to chromosomal translocations that bring the MYC gene under the control of a super-enhancer.

282 nesis in a transgenic model expressing the c-myc gene under the MMTV-LTR promoter.

283 C/Grb2/MAPK and STAT6 pathways and through c-myc gene up-regulation.

284 In vitro binding to the c-myc gene was abolished after deletion of the N-terminal

285 a 280-base pair region in intron 1 of the c-myc gene was explored.

286 Whereas overexpression of the c-myc gene was found to promote apoptosis in fibroblasts,

287 ng fluorescence in situ hybridization, the c-myc gene was localized to hamster chromosome 6qb.

288 sis showed that the induction of egr-1 and c-myc genes was associated with a transient recruitment of

289 d to suppress polymerase elongation on the c-myc gene, we employed the chromatin immunoprecipitation

290 utations of the 5' noncoding region of the c-myc gene were demonstrated in 3 other cases (19%), altho

291 TBLV insertions near the c-myc gene were detectable in 2 of 30 tumors tested, where

292 lated E2F sites derived from the c-myb and c-myc genes whereas both E2F1 and E2F3 fail to transactiva

293 Two other v-Myc genes which carry a mutation at thr-61 (avian MH2) o

294 IRF4) directly regulates expression of the c-Myc gene, which is not only associated with various B ce

295 catenin/TCF4-mediated transcription of the c-myc gene, which was caused by GLIPR1-mediated redistribu

296 Histone hyperacetylation of control c-myc genes, which was induced by the deacetylase inhibito

297 l evidence implicates amplification of the N-myc gene with aggressive tumor growth and poor outcome i

298 aried size and/or position relative to the N-myc gene, with DDX1 representing at least one other gene

299 ults in the decreased levels of GATA-1 and c-myc genes, with an accompanying induction of apoptosis.

300 Active and inactive c-myc genes yielded different patterns of S1 nuclease and