ライフサイエンスコーパス: NHEJ

1 NHEJ relies on Ku to thread onto DNA termini and thereby

2 NHEJ relies on polynucleotide kinase/phosphatase (PNKP),

3 Here we have developed a NHEJ reconstitution system that includes the nuclease, p

4 ergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S-S ju

5 amage response and inappropriate repair by A-NHEJ.

6 omote joining of de-protected telomeres by A-NHEJ.

7 ewly replicated telomeres from engaging in A-NHEJ mediated fusions that would otherwise promote genom

8 ic alternative non-homologous end joining (A-NHEJ) pathway.

9 he alternative non-homologous end-joining (A-NHEJ), which relies on PARP1 and LIG3.

10 t residues, limit the efficiency of accurate NHEJ by Polmu in vitro and in vivo.

11 lease accessibility, and recruits additional NHEJ factors, including Nej1 and Lif1.

12 verhang polarity of chromosomal DSBs affects NHEJ, we made site-specific 5'-overhanging DSBs (5' DSBs

13 In Top-less cells, the protection against NHEJ is alleviated if the expression of the TRF2-interac

14 and exonuclease activities and inhibits alt-NHEJ using non-enzymatic functions.

15 ckdown of alt-nonhomologous end joining (alt-NHEJ) components-XRCC1, LIG3, and PARP1-suppresses stres

16 ection prior to repair by c-NHEJ and not alt-NHEJ.

17 We show that WRN regulates alt-NHEJ and shields DSBs from MRE11/CtIP-mediated resection

18 Thus, alt-NHEJ, which contributes to genetic mutability in cancer

19 This resistance is independent of alternate-NHEJ and is instead achieved by re-activation of HR.

20 modification of the DNA break by alternative NHEJ prevents further Cas9 cutting, generating a heterog

21 ogy, here we show that repair by alternative NHEJ yields non-TTAGGG nucleotide insertions at fusion b

22 tectable, microhomology-mediated alternative NHEJ efficiently repairs DSBs in mitochondria.

23 However, a mutagenic alternative NHEJ pathway, microhomology-mediated end joining (MMEJ),

24 o intercept the more error-prone alternative NHEJ repair pathway by recruiting Ku and associated NHEJ

25 Polq inhibition suppresses alternative NHEJ at dysfunctional telomeres, and hinders chromosomal

26 inter-chromosomal, as opposed to alternative NHEJ-mediated intra-chromosomal, telomere fusions and ev

27 ed NBS1(S432) with TRF2 promotes alternative-NHEJ repair of telomeres lacking POT1-TPP1.

28 formation, inhibits both ATM activation and NHEJ.

29 The BRCA and NHEJ pathways are required for the repair of CX-5461 and

30 on of homology-directed repair-dependent and NHEJ-dependent genome-editing tools comprises a powerful

31 e lack of a simple method to measure HDR and NHEJ directly and simultaneously at endogenous loci.

32 Accordingly, HR and NHEJ compete for repair of these paired nicks, but, surp

33 approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for D

34 unctional switch in selecting between HR and NHEJ pathways.

35 nism modulates pathway choice between HR and NHEJ via displacement of the Ku heterodimer from DSBs to

36 tic lethal relationship between DEK loss and NHEJ inhibition.

37 e components of homologous recombination and NHEJ, which have no effect.

38 r cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the

39 largely based on 5' to 3' DNA resection, and NHEJ proceeds only if resection has not been initiated.

40 in a pathway termed Archaeo-Prokaryotic (AP) NHEJ that facilitates DSB repair.

41 for DNA strand displacement synthesis in AP-NHEJ, revealing the mechanisms that enable Pol and PE to

42 Archaeal NHEJ polymerases (Pol) are capable of strand displacemen

43 However, an associated NHEJ phosphoesterase (PE) resects these products to ensu

44 pair pathway by recruiting Ku and associated NHEJ factors.

45 structural conservation with their bacterial NHEJ counterparts.

46 To address this, we employed a plasmid-based NHEJ DNA repair screen in budding yeast (Saccharomyces c

47 ne silencing (VIGS) of Nicotiana benthamiana NHEJ genes, and by biochemical assays for T-DNA integrat

48 BRCA1, leading to pathway selection between NHEJ and homologous recombination.

49 ed in hyper-resection, which attenuated both NHEJ and HR and severely compromised DSB repair resultin

50 repaired with similar kinetics, employ both NHEJ and HR, and can use homologous chromosomes as an HR

51 p53 ablation and irrevocably deregulated by NHEJ inactivation.

52 a mechanism for iterative repair of DSBs by NHEJ.

53 t UNC-84 both alters the extent of repair by NHEJ and promotes the processing of cross-links by FAN-1

54 53BP1, which influences DSB repair by NHEJ, colocalizes with human BUB1 and is recruited to th

55 or addition, explaining why DSBs repaired by NHEJ are rarely restored to their original DNA sequence.

56 confirm that 53BP1 status does not affect c-NHEJ.

57 (C-NHEJ)-deficient NSPCs reveals that both C-NHEJ and alternative end-joining pathways can generate t

58 site, undergo resection prior to repair by c-NHEJ and not alt-NHEJ.

59 oes not commence, then repair can ensue by c-NHEJ, but when executed, Artemis is essential to complet

60 While MMEJ is suppressed by C-NHEJ, the relationship between HR and MMEJ is less clear

61 tely engineered genomic sites, compromises c-NHEJ and markedly increases cell killing and translocati

62 complex substitutes in vitro for the core c-NHEJ factor, XLF.

63 Thus, PAXX provides core C-NHEJ factor-associated functions in the absence of XLF a

64 Core C-NHEJ factors, such as XRCC4, are required for joining DS

65 Resection-dependent c-NHEJ represents an inducible process during which Plk3 p

66 Resection-dependent c-NHEJ significantly contributes to the formation of delet

67 essential to complete resection-dependent c-NHEJ.

68 NA repair profiles into contributions from c-NHEJ and MMEJ.

69 ) repair and genomic stability not only in c-NHEJ-proficient but also -deficient human G1-phase cells

70 ect to potential PAXX and XLF functions in C-NHEJ.

71 viding important mechanistic insights into C-NHEJ-mediated error-free DSBR of the transcribed genome.

72 Classical nonhomologous end joining (C-NHEJ) is a major mammalian DNA double-strand break (DSB)

73 Classical non-homologous end-joining (C-NHEJ) is the dominant pathway for DSB repair (DSBR) in a

74 ways [canonical nonhomologous end joining (C-NHEJ) or alternative end joining (ALT-EJ)], which cause

75 the classical non-homologous end-joining (C-NHEJ) pathway dependent on Ku70/80 and LIG4, or the alte

76 a the canonical nonhomologous end joining (c-NHEJ) pathway.

77 Canonical non-homologous end joining (c-NHEJ) repairs DNA double-strand breaks (DSBs) in G1 cell

78 s is classical non-homologous end-joining (C-NHEJ) which relies on Ku binding to DNA ends and DNA Lig

79 the classical non-homologous end joining (C-NHEJ), or homologous recombination (HR) pathways.

80 ersus classical nonhomologous end-joining (C-NHEJ)-deficient NSPCs reveals that both C-NHEJ and alter

81 uring classical nonhomologous end joining (C-NHEJ).

82 ns by classical nonhomologous end joining (C-NHEJ).

83 we report that during such DSBR, mammalian C-NHEJ proteins form a multiprotein complex with RNA polym

84 Whereas classical NHEJ (C-NHEJ) is undetectable, microhomology-mediated alternativ

85 id could be recovered from control but not C-NHEJ factor-depleted cells, providing important mechanis

86 Depletion of C-NHEJ factors significantly abrogates DSBR in transcribed

87 inase may affect the relative influence of C-NHEJ vs. ALT-EJ on rearrangement formation.

88 rangement junctions that show hallmarks of C-NHEJ.

89 nonhomologous end-joining repair pathway (c-NHEJ), regenerating the target site.

90 It promotes c-NHEJ via helicase and exonuclease activities and inhibit

91 Finally, several C-NHEJ factors are required for the increase in rearrangem

92 We indeed found pre-mRNA in the C-NHEJ complex.

93 as an XLF homodimer) fully complements the c-NHEJ deficits of some XLF-deficient cell strains but not

94 We suggest that the contribution of the C-NHEJ pathway to the formation of a 0.4-Mbp deletion rear

95 onucleolytic degradation and repair by the c-NHEJ pathway.

96 ion in an experimental condition, in which C-NHEJ is the predominant EJ repair event (i.e., expressio

97 The XRCC4-like-factor (XLF) C-NHEJ protein is dispensable for V(D)J recombination in n

98 ination process that relies on the classical NHEJ machinery.

99 Whereas classical NHEJ (C-NHEJ) is undetectable, microhomology-mediated al

100 ational signatures associated with classical NHEJ-mediated inter-chromosomal, as opposed to alternati

101 Classical-NHEJ-mediated repair of telomeres lacking TRF2 requires

102 Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA

103 report that RECQL4 promotes and coordinates NHEJ and HR in different cell cycle phases.

104 ng to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase cata

105 sing the recruitment of 53BP1, and decreases NHEJ, rendering cells more sensitive to DSBs.

106 egg extracts via the canonical, Ku-dependent NHEJ pathway.

107 tingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocatio

108 two stages that are controlled by different NHEJ factors.

109 ce of a decreased template dependency during NHEJ, which renders the error-rate of the mutants higher

110 s to recruit and/or stimulate enzymes during NHEJ.

111 ferentially used for filling DNA gaps during NHEJ partly depends on sequence complementarity at the b

112 mplementary functions of PAXX and XLF during NHEJ.

113 a domain of Polmu for accurate and efficient NHEJ, but also its contribution to the error-prone behav

114 nous Mcl-1 depletion reduced HR and enhanced NHEJ, Mcl-1 overexpression resulted in a net increase in

115 ells harboring the nej1-V338A mutant exhibit NHEJ-mediated repair deficiencies and hyper-resection 0.

116 ation with the Ku70/80 complex to facilitate NHEJ repair.

117 Defective CSR was linked to failed NHEJ and residual A-EJ access to unrepaired double-stran

118 e in eukaryotic cells and functions to favor NHEJ over HDR by suppressing end resection, which is the

119 cooperative assembly of an extended flexible NHEJ core complex that supports APLF accessibility while

120 NA-PK), and X4L4 within an extended flexible NHEJ core complex.

121 y, we found that DNA ligase 4, essential for NHEJ, did not make a significant contribution to palindr

122 e phosphorylation sites are not required for NHEJ.

123 (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of t

124 In contrast to the absolute requirement for NHEJ to resolve DSBs associated with V(D)J recombination

125 While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis

126 Surprisingly, the HDR/NHEJ ratios were highly dependent on gene locus, nucleas

127 re, through systematic analysis of the human NHEJ factor interactome, we identify PAXX as a direct in

128 ling based on overhang polarity that impacts NHEJ kinetics and fidelity through differential recruitm

129 Depletion of PP1 impairs NHEJ in both Xenopus egg extracts and human cells.

130 Importantly, NHEJ instead of alternative end-joining (A-EJ) was revea

131 mpete with canonical repair pathways but, in NHEJ-deficient cells, is engaged more frequently and pro

132 dence demonstrating the observed decrease in NHEJ is insufficient to impact immunoglobulin class swit

133 repair of DNA double-strand breaks (DSBs) in NHEJ, it is essential in opening the DNA hairpin interme

134 DSBs associated with CSR can be resolved in NHEJ-deficient cells (albeit at a reduced level) by a po

135 e DNA repair protein Ku is the first step in NHEJ, followed by the iterative binding of nucleases, DN

136 ore, knockdown of UBE2S expression inhibited NHEJ-mediated DSB repair and rendered glioblastoma cells

137 Concurrently inhibiting NHEJ with SCR7 does not increase HDR or improve gene tar

138 T analysis of the Ku/XRCC4/XLF/DNA ligase IV NHEJ ligation complex, that end-to-end synapsis involves

139 repair pathways, non-homologous end joining (NHEJ) and homologous recombination (HR).

140 ckout alleles via nonhomologous end joining (NHEJ) and knock-in alleles via homology-directed repair

141 ected repair and non-homologous end joining (NHEJ) are the two major DSB repair pathways that are hig

142 -strand breaks by nonhomologous end joining (NHEJ) are two related family X DNA polymerases, Pol lamb

143 alternative (alt)-nonhomologous end joining (NHEJ) during DNA double-strand break (DSB) repair.

144 H29 could inhibit nonhomologous end joining (NHEJ) efficiency and that no HR activity was detected in

145 (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer bind

146 Non-homologous end joining (NHEJ) involves limited processing, but homology-dependen

147 Non-homologous end joining (NHEJ) is a major DNA double-strand break (DSB) repair me

148 Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand bre

149 Non-homologous end joining (NHEJ) is the main repair pathway for DNA double-strand b

150 preponderance of non-homologous end joining (NHEJ) mediated repair events over homology directed repa

151 that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will i

152 ed by either the non-homologous end joining (NHEJ) or homologous recombination (HR) pathway.

153 activation of the nonhomologous end joining (NHEJ) pathway.

154 the error-prone non-homologous end joining (NHEJ) pathway.

155 teins involved in nonhomologous end joining (NHEJ) repair restrict amplification of viral DNA.

156 h are involved in nonhomologous end joining (NHEJ) repair, enhance amplification of viral DNA.

157 e attenuation of non-homologous end joining (NHEJ) repair, the role of DEK in DNA repair remains inco

158 Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling eu

159 ole in mediating non-homologous end joining (NHEJ), a major repair pathway for DNA double-strand brea

160 s via error-prone nonhomologous end joining (NHEJ), but the efficiency of precise sequence replacemen

161 ch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand cro

162 s telomeres from non-homologous end joining (NHEJ), plays important roles in telomere length control

163 in human cells, non-homologous end joining (NHEJ), rejoins broken DNA ends by direct ligation.

164 tral component of nonhomologous end joining (NHEJ), repairing DNA double-strand breaks that would oth

165 In contrast to non-homologous end joining (NHEJ), TMEJ efficiently repairs end structures expected

166 break repair and non-homologous end joining (NHEJ).

167 e inactivation of nonhomologous end joining (NHEJ).

168 rsus alternative, nonhomologous end joining (NHEJ).

169 ination (HR) and non-homologous end joining (NHEJ).

170 tion (HR) and the nonhomologous end joining (NHEJ).

171 repair (HDR) and non-homologous end joining (NHEJ).

172 mbination (HR) or nonhomologous end joining (NHEJ).

173 elomeres against non-homologous end joining (NHEJ).

174 he efficiency of non-homologous end joining (NHEJ).

175 tors involved in non-homologous end joining (NHEJ).

176 nation (HDR) and non-homologous end joining (NHEJ).

177 ntly repaired by non-homologous end joining (NHEJ).

178 repair pathways, nonhomologous end-joining (NHEJ) and homologous recombination (HR), is regulated by

179 d breaks (DSBs): non-homologous end-joining (NHEJ) and homologous recombination (HR).

180 y TDP2-dependent non-homologous end-joining (NHEJ) but whether this promotes or suppresses translocat

181 RADD facilitates non-homologous end-joining (NHEJ) by recruiting NHEJ repair factors 53BP1 and Ku70/8

182 omponents of the non-homologous end-joining (NHEJ) complex and participated in the NHEJ-mediated DNA

183 not suppressed by nonhomologous end-joining (NHEJ) components, arguing that nick processing does not

184 ion of the XRCC4 non-homologous end-joining (NHEJ) DNA repair gene and p53 efficiently induces brain

185 ption induced by non-homologous end-joining (NHEJ) DNA repair offers a potential treatment option for

186 mutations in the nonhomologous end-joining (NHEJ) DNA repair protein DNA ligase IV (LIG4) lead to im

187 t presumably from nonhomologous end-joining (NHEJ) events before the segregation of somatic and germ-

188 As the non-homologous end-joining (NHEJ) factor, Ku70/80 (Ku), is quickly recruited to DSBs

189 assembly of core nonhomologous end-joining (NHEJ) factors on damaged chromatin in cells.

190 Nonhomologous end-joining (NHEJ) is the major DNA double-strand break (DSB) repair

191 In humans, nonhomologous DNA end-joining (NHEJ) is the major pathway by which DNA double-strand br

192 Non-homologous end-joining (NHEJ) is the most prominent DNA double strand break (DSB

193 Nonhomologous DNA end-joining (NHEJ) is the predominant double-strand break (DSB) repai

194 coexpression the nonhomologous end-joining (NHEJ) machinery from the closely related archaeon, Metha

195 The nonhomologous DNA end-joining (NHEJ) pathway is a key mechanism for repairing dsDNA bre

196 The nonhomologous end-joining (NHEJ) pathway is the primary repair pathway for DNA doub

197 The non homologous end-joining (NHEJ) pathway of double-strand break (DSB) repair often

198 The non-homologous end-joining (NHEJ) pathway repairs DNA double-strand breaks (DSBs) in

199 nation (HR) or by nonhomologous end-joining (NHEJ) pathways.

200 ly eliminating Ku nonhomologous end-joining (NHEJ) protein, indicating that Ctp1-dependent clipping b

201 FBXW7 facilitates nonhomologous end-joining (NHEJ) repair and that FBXW7 depletion causes radiosensit

202 leles created by non-homologous end-joining (NHEJ) repair of double-stranded DNA breaks generated by

203 bination (HR) and nonhomologous end-joining (NHEJ) repair pathways, with defective localization of Br

204 R) and decreased non-homologous end-joining (NHEJ) repair, suggesting that Wwox contributes to DNA DS

205 ally repaired by non-homologous end-joining (NHEJ) resulting in nonspecific insertions, deletions or

206 tant decrease in non-homologous end-joining (NHEJ), accounting for the improvement in cellular growth

207 However, nonhomologous end-joining (NHEJ), an error-prone repair, acts concurrently, reducin

208 combination (HR), nonhomologous end-joining (NHEJ), and microhomology-mediated end-joining (MMEJ).

209 nt components and nonhomologous end-joining (NHEJ), but not homologous recombination.

210 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes T

211 hrough repair by non-homologous end-joining (NHEJ).

212 ination (HR) and non-homologous-end-joining (NHEJ).

213 hways, including non-homologous end-joining (NHEJ).

214 epair via MMEJ or nonhomologous end-joining (NHEJ).

215 us, T-DNA integration does not require known NHEJ proteins, suggesting an alternative route for integ

216 hich shares structural similarity with known NHEJ factors-XRCC4 and XLF.

217 ange resection altogether, thereby licensing NHEJ at collapsed forks.

218 tion of DNA-PKcs after DNA damage to mediate NHEJ.

219 re required for Mcl-1 to inhibit Ku-mediated NHEJ.

220 mbination, as effected by Ku70/Ku86-mediated NHEJ.

221 nd catalytic activity, impairs Tdp2 mediated NHEJ of tyrosine blocked termini, and renders cells sens

222 53BP1 impacts physiological versus mutagenic NHEJ.

223 tor, 26 PPIs in DDR pathways (BER, MMR, NER, NHEJ, HR, TLS, and ICL repair) are specifically discusse

224 Altogether, our data identify PAXX as a new NHEJ factor and provide insight regarding the organizati

225 PAXX is the newest NHEJ factor, which shares structural similarity with kno

226 abidopsis thaliana roots mutant for numerous NHEJ and other related genes.

227 While we predictably observed NHEJ to be the predominant pathway for DSB repair in our

228 nt for L4 and is critical for the ability of NHEJ factors to promote stable pairing of ends.

229 that RECQL4 modulates the pathway choice of NHEJ and HR in a cell cycle-dependent manner.

230 Repair is mediated by a core complex of NHEJ factors that includes a ligase (DNA Ligase IV; L4)

231 prominent than that seen in deficiencies of NHEJ factors ARTEMIS and DNA-dependent protein kinase ca

232 To promote HDR at the expense of NHEJ, we targeted DNA ligase IV, a key enzyme in the NHE

233 at explain genetic and molecular features of NHEJ and V(D)J recombination within cells.

234 ors can alter the efficiency and fidelity of NHEJ.

235 Inactivation of NHEJ supresses the sensitivity of exo1- cells to PARPi,

236 in DNA repair through both the inhibition of NHEJ and the promotion of homologous recombination at si

237 of certain cancers, suggesting that loss of NHEJ may be selected in some malignancies and that the d

238 rovide insight regarding the organization of NHEJ factors responding to diverse types of DSB ends.

239 SBs, consistent with a robust recruitment of NHEJ proteins to 5' DSBs.

240 we show that CYREN (cell cycle regulator of NHEJ) is a cell-cycle-specific inhibitor of cNHEJ.

241 pathway and play a key role in conferring on NHEJ the flexibility required for accurate and efficient

242 ay that can simultaneously detect one HDR or NHEJ event out of 1,000 copies of the genome.

243 eak repair when resection is misregulated or NHEJ is compromised.

244 ecide if an end is channeled to resection or NHEJ is not well understood.

245 A-PKcs for targeted phosphorylation of other NHEJ proteins as well as trans-phosphorylation of DNA-PK

246 ' overhangs without the involvement of other NHEJ proteins.

247 nized by Ku, which then interacts with other NHEJ proteins to improve their affinity at DNA ends.

248 enome-editing conditions that favor HDR over NHEJ has been hindered by the lack of a simple method to

249 ession resulted in a net increase in HR over NHEJ.

250 l dominance of homologous recombination over NHEJ pathways in the moss, contrary to the inverse situa

251 of these archaeal (Methanocella paludicola) NHEJ nuclease and polymerase enzymes, demonstrating thei

252 s) by the nonhomologous end-joining pathway (NHEJ) is important not only for repair of spontaneous br

253 the non-homologous DNA end-joining pathway (NHEJ).

254 t that PAXX is dispensable for physiological NHEJ in otherwise wild-type mice.

255 res appears as a backup mechanism to prevent NHEJ when topology-mediated telomere protection is impai

256 RECQL4 interacts with Ku70 to promote NHEJ in G1 when overall cyclin-dependent kinase (CDK) ac

257 lso recruited to DNA damage sites to promote NHEJ.

258 rone, and they predict increased error-prone NHEJ activity and A-EJ suppression as the cause of the d

259 -homologous end-joining (NHEJ) by recruiting NHEJ repair factors 53BP1 and Ku70/80 complex, whereas T

260 d53 loss-of-function mutant and show reduced NHEJ efficiency, with a drastic failure to up-regulate R

261 t abrogates XRCC4 polyubiquitylation reduces NHEJ repair.

262 y, the entire complement of genes regulating NHEJ remains unknown.

263 , and ligase components to evaluate relative NHEJ efficiency and analyze ligated junctional sequences

264 emonstrate that Lig4(R278H) activity renders NHEJ to be more error-prone, and they predict increased

265 s not directly involved in DNA break repair (NHEJ).

266 e find that CSB facilitates HR and represses NHEJ.

267 Furthermore, mutation of required NHEJ factor DNA Ligase 4 results in enhanced haploid rec

268 f DNA-PK (DNA-PKcs) is a vertebrate-specific NHEJ factor that can be autophosphorylated or transphosp

269 OX, in which Brca1-Wwox interaction supports NHEJ as the dominant DSB repair pathway in Wwox-sufficie

270 reveal a pivotal role for Akt in suppressing NHEJ and highlight the tight connection between aberrant

271 often than HDR, we found that more HDR than NHEJ was induced under multiple conditions.

272 These observations demonstrate that NHEJ contributes to p53-mediated glioblastoma suppressio

273 Next-generation sequencing revealed that NHEJ at 5' DSBs had a higher mutation frequency, and val

274 Although it is widely thought that NHEJ generally occurs more often than HDR, we found that

275 The NHEJ-dependent mutations included deletions ranging from

276 modulate the bridging of broken ends by the NHEJ core complex.

277 ermini that are critical for ligation by the NHEJ DNA ligase, LigIV.

278 s in LIG4 and XRCC4, which together form the NHEJ ligation complex.

279 Mutations in the NHEJ factor XLF result in extreme sensitivity for ionizi

280 targeted DNA ligase IV, a key enzyme in the NHEJ pathway, using the inhibitor Scr7.

281 ining (NHEJ) complex and participated in the NHEJ-mediated DNA repair process.

282 mini and thereby improve the affinity of the NHEJ enzymatic components consisting of polymerases (Pol

283 It remains unclear how components of the NHEJ machinery assemble a synaptic complex that bridges

284 ings identify PAXX as a new component of the NHEJ machinery.

285 Mutations in several components of the NHEJ pathway have been identified, often associated with

286 NA ligase IV (Lig4), a core component of the NHEJ pathway, reduces CSR efficiency in a mouse B-cell l

287 937 cells, suggesting that repression of the NHEJ repair pathway may be involved in COH29-induced DSB

288 PNKP and LigIV require the NHEJ scaffolding protein, XRCC4.

289 Therefore, the NHEJ machinery exhibited a strong preference for precise

290 onstrated the degrees of importance of these NHEJ proteins in the mechanism of repair of dsDNA breaks

291 t 3' overhangs, favoring the view that these NHEJ proteins are sequentially rather than concurrently

292 tensively to engineer gene knockouts through NHEJ, editing by HDR remains inefficient and can be corr

293 Thus, NHEJ is a single pathway with multiple enzymes at its di

294 mal nucleotides are efficiently channeled to NHEJ, ends with damaged nucleotides or bulky adducts are

295 surement of relative activity of MMEJ versus NHEJ.

296 rter gene, demonstrating gene disruption via NHEJ in vivo.

297 two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects.

298 ckout cells were sensitive to apoptosis with NHEJ inhibition.

299 In vitro studies with NHEJ proteins have been performed to evaluate the nucleo

300 egulate PNKP recruitment and activity within NHEJ.