ライフサイエンスコーパス: synthetic lethality

1 ecules (dubbed "fully small-molecule-induced synthetic lethality").

2 omimetic ABT737, through non-BCL-2-dependent synthetic lethality.

3 rsensitive to PARPi through the mechanism of synthetic lethality.

4 the glycine cleavage (GCV) system caused the synthetic lethality.

5 leta, polzeta and pold3 mutations results in synthetic lethality.

6 may be informed by a deeper understanding of synthetic lethality.

7 ynergizes with olaparib (a PARPi) to trigger synthetic lethality.

8 iding the first anti-cancer therapy based on synthetic lethality.

9 th oncogenic Raf or Ras induces acidosis and synthetic lethality.

10 eutic approaches that exploit the concept of synthetic lethality.

11 ting these compensatory pathways may produce synthetic lethality.

12 ame as a top candidate gene for camptothecin synthetic lethality.

13 asmic chaperone in E. coli, SurA, results in synthetic lethality.

14 loit oncogene and non-oncogene addiction and synthetic lethality.

15 s in cases where mutual exclusivity reflects synthetic lethality.

16 ly, simultaneous ATM and HUS1 defects caused synthetic lethality.

17 ess nonstop proteins may not be the cause of synthetic lethality.

18 (PARP-1) inhibition based on the concept of synthetic lethality.

19 h cellular proliferation, a concept known as synthetic lethality.

20 ) polymerase (PARP) inhibitor ABT-888 due to synthetic lethality.

21 ombination (HR) genes BRCA1 or BRCA2 through synthetic lethality.

22 cells, confirming the proposed mechanism of synthetic lethality.

23 of cdc28(CST) and cak1 mutations results in synthetic lethality.

24 on with PARP inhibition can similarly induce synthetic lethality.

25 r novel cancer treatment strategies based on synthetic lethality.

26 that confirmed the redundancy explanation of synthetic lethality.

27 ting the "compensation" explanation for this synthetic lethality.

28 findings provide insights into the causes of synthetic lethality.

29 behind chemosensitization and the concept of synthetic lethality.

30 '-blocking lesions relevant to APEX2-BRCA1/2 synthetic lethality.

31 r HER2 through the induction of proteostatic synthetic lethality.

32 utic approaches by exploiting the concept of synthetic lethality.

33 cid and carnosic acid were the cause for the synthetic lethality.

34 s to widespread DNA double-strand breaks and synthetic lethality.

35 N-mediated metabolic reprogramming, leads to synthetic lethality.

36 linically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a

37 s are promising therapeutic agents that show synthetic lethality against many types of cancer (includ

38 cancers, making fully small-molecule-induced synthetic lethality an innovative approach toward unmet

39 onditionally accumulate stalled forks caused synthetic lethality, an effect indistinguishable from E.

40 Synthetic lethality-an interaction between two genetic e

41 Diploid synthetic lethality analysis by microarray (dSLAM) using

42 mple, both synthetic genetic array (SGA) and synthetic-lethality analysis by microarray (SLAM) method

43 e-wide synthetic lethality screens, known as synthetic lethality analyzed by microarray (SLAM).

44 Such addictions, synthetic lethalities and other tumor vulnerabilities ha

45 Synthetic lethality and collateral lethality are two wel

46 ehydrogenase (GPDH1) exhibit growth defects, synthetic lethality and decreased glycolytic flux.

47 er cells to a DNA repair pathway is based on synthetic lethality and has wide applicability to the tr

48 ssion of hyper-recombination, suppression of synthetic lethality and heteroduplex rejection.

49 Delineation of the mechanisms underlying synthetic lethality and identification of treatment resp

50 econd-site suppressor of sgs1Delta slx5Delta synthetic lethality and identified it as an allele of th

51 GrxD to uncover the molecular basis of this synthetic lethality and observed that GrxD can form FeS-

52 The strategy could be used to search for synthetic lethality and optimise combination protocol de

53 as a potential therapeutic target to promote synthetic lethality and overcome chemoresistance.

54 synthesis, suppress the dun1Delta pol2-M644G synthetic lethality and restore the mutator phenotype of

55 ndidate for topoisomerase 1 (TOP1) inhibitor synthetic lethality and showed that ATR inhibition sensi

56 lls to PARPi, indicating this pathway drives synthetic lethality and that in its absence alternative

57 rtheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical approval p

58 -SUMO chains, suppressed sgs1Delta slx5Delta synthetic lethality and the slx5Delta sporulation defect

59 taxia telangiectasia mutated (ATM) result in synthetic lethality and, in the mouse, early embryonic d

60 i, inactivation of RNase H2 and RAD52 led to synthetic lethality, and combined loss of RNase H2 and R

61 ne particular type of gene-gene interaction, synthetic lethality, and find that the accuracy rate is

62 This review discusses recent developments in synthetic lethality anticancer therapeutics, including p

63 omarkers will be critical for the success of synthetic lethality anticancer therapy.

64 t Chinese hamster and human cancer cells for synthetic lethality application using double-strand brea

65 ficiency could also be exploited for a novel synthetic lethality application using DSB repair inhibit

66 ced DNA damage as the base for a conditional synthetic lethality approach.

67 gregation, represents a novel target for the synthetic lethality approach.

68 Using synthetic lethality approaches, we identified molecular

69 mics and functional genomic screens (such as synthetic lethality) are providing mechanisms to rapidly

70 Finally, we identify synthetic lethality arising from gene overactivation and

71 Here, we describe the concept of augmented synthetic lethality (ASL): depletion of a third gene pro

72 Accordingly, validation was achieved through synthetic lethality assays in which RNAi-mediated silenc

73 utants lacking both Ptp4E and Ptp10D display synthetic lethality at hatching owing to respiratory fai

74 ivation of Fancd2 and Mlh1 did not result in synthetic lethality at the cellular level.

75 ed that altered genome integrity might allow synthetic lethality-based options for targeted therapeut

76 f prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in v

77 Further analysis identified synthetic lethality between an elf1Delta mutation and mu

78 this is a conserved function underlying the synthetic lethality between ARID1A and ARID1B.

79 this is the first data set to demonstrate a synthetic lethality between ARID1A mutation and EZH2 inh

80 insight into the molecular mechanisms of the synthetic lethality between BRCA2 and PARP1.

81 The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F

82 Overall, we conclude that the synthetic lethality between clb5 and bub1 or bub3 is lik

83 Here, we identified synthetic lethality between decreased activity of cyclin

84 DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-

85 lso, there is evidence for a relationship of synthetic lethality between NRAS and BRAF oncogenes that

86 We use synthetic lethality between paralog genes to show that g

87 A1/2 mutant cancers validated the concept of synthetic lethality between PARP inhibition and deleteri

88 Synthetic lethality between poly(ADP-ribose) polymerase

89 taining complexes may be responsible for the synthetic lethality between ppr2Delta and taf14Delta, we

90 Building on the observed synthetic lethality between Rb1 and Skp2, we found that

91 These results suggest that synthetic lethality between ROCK inhibition and VHL defi

92 The synthetic lethality between spo7Delta and mps3 mutants w

93 ic genetic array (SGA) analysis, testing for synthetic lethality between the clb5 deletion and a sele

94 tion with novel protein partners and unravel synthetic lethality between XRN2 depletion and PARP1 inh

95 of CHK1 and PI3K/mTOR pathways yields potent synthetic lethality by causing lethal replication stress

96 2 inhibition and contributed to the observed synthetic lethality by inhibiting PI3K-AKT signaling.

97 The exploitation of synthetic lethality by small-molecule targeting of pathw

98 Several of these synthetic lethalities can be suppressed by overexpressio

99 Synthetic lethality can also be achieved "chemically" by

100 igh-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosom

101 Recessive synthetic lethality can result in high-frequency X-linke

102 Thus, sgs1Delta slx5Delta synthetic lethality cannot be due simply to high levels

103 ranscription factor mutations, including the synthetic lethality caused by combining an spt16 mutatio

104 or E. coli genetic interactions reported the synthetic lethality (combination of mutations leading to

105 cient status predisposing to RAD52-dependent synthetic lethality could be predicted by genetic abnorm

106 In most cases, synthetic lethality depends upon hyperacetylation of H3

107 Furthermore, analysis of synthetic lethality effects and examination of the activ

108 demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired c

109 Notably, elevated genomic instability and synthetic lethality following suppression of ATR were no

110 bnormalities in multiple signaling pathways, synthetic lethality for a specific tumor suppressor gene

111 escribe a potential utility of PARPi-induced synthetic lethality for leukemia treatment and reveal a

112 53 and PIP4K2B were not viable, indicating a synthetic lethality for loss of these two genes.

113 Using analysis of concordance for synthetic lethality for the yeast sphingolipid phospholi

114 Conceptually, synthetic lethality holds the promise of identifying non

115 scuss the biological rationale for BRCA-PARP synthetic lethality, how the synthetic lethal approach i

116 optimized AsCas12a toolkit by screening for synthetic lethalities in OVCAR8 and A375 cancer cells, d

117 terioration of the intestinal epithelium and synthetic lethality in adult mice.

118 leads to increased micronuclei formation and synthetic lethality in ALT cells.

119 ribose) polymerase (PARP) inhibitor, induced synthetic lethality in BRCA-deficient cells.

120 lanine 79 [F79]) as a valid target to induce synthetic lethality in BRCA1- and/or BRCA2-deficient leu

121 DP-ribose) polymerase inhibitor that induces synthetic lethality in BRCA1- or BRCA2-deficient cells,

122 , rosemary extract is hypothesized to induce synthetic lethality in BRCA2 deficient cells by PARP inh

123 e) polymerase (PARP) inhibitors can generate synthetic lethality in cancer cells defective in homolog

124 p53 GOF mutants, inhibition of which causes synthetic lethality in cancer cells expressing p53 GOF m

125 re we show that centrosome depletion induces synthetic lethality in cancer cells that contain the 17q

126 cuss the connection between G4 formation and synthetic lethality in cancer cells, and recent progress

127 The first clinical exemplification of synthetic lethality in cancer has been the exploitation

128 package DiscoverSL to predict and visualize synthetic lethality in cancers using multi-omic cancer d

129 n-of-function (GOF) alleles that exhibit (1) synthetic lethality in combination with mutations in BMP

130 d OXPHOS inhibitor metformin (MET), both for synthetic lethality in culture and for inhibition of tum

131 se) polymerase (PARP) inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells.

132 hese findings can be exploited for eliciting synthetic lethality in metabolically stressed cancer cel

133 e inhibitors were developed with the idea of synthetic lethality in mind, a concept from classical ge

134 HK2-ASO1/DPI/PER triple-combination achieved synthetic lethality in multiple myeloma cells in culture

135 Combining MYC blockade with PARPi yielded synthetic lethality in MYC-driven TNBC cells.

136 trant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft

137 ATR and conventional therapies might promote synthetic lethality in p53-deficient tumors, and thus mi

138 ive PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with lo

139 targeting of PARP1 resulted in dual cellular synthetic lethality in quiescent and proliferating immat

140 2(shRNA) knockdown and are also sensitive to synthetic lethality in response to the combination of HK

141 We validate SINaTRA by predicting synthetic lethality in S. pombe using S. cerevisiae data

142 omosome loss, chromosome missegregation, and synthetic lethality in srs2Delta.

143 ry path amongst targeted genes or to analyse synthetic lethality in the context of anticancer therapy

144 based methodology that discovers genome-wide synthetic lethality in translation between species.

145 n and PARP-mediated DNA repair yields potent synthetic lethality in triple-negative breast tumors and

146 2, Bcl-xL, and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy.

147 selective targeting of HSPA1B could produce synthetic lethality in tumors that display HSPA1A promot

148 he repair of single stranded breaks, causing synthetic lethality in tumors with loss of high-fidelity

149 he combined loss of Ikzf1 and Gata1 leads to synthetic lethality in vivo associated with prominent de

150 y, our results suggest a molecular basis for synthetic lethality in which hlh-1 and unc-120 mutant ph

151 Inhibition of such a pathway could cause "synthetic lethality" in adapted cells while not markedly

152 The genetic concept of synthetic lethality, in which the combination or synthes

153 High copy suppressors of this synthetic lethality included three mannosyltransferases,

154 Synthetic lethality induced by both PME-1 and HDAC4 inhi

155 Finally, we found that synthetic lethality induced by TXNRD1 and AKT inhibitors

156 Furthermore, we found that the synthetic lethality interaction between the TXNRD1 and A

157 Consistently, hst3 hst4 cells display synthetic lethality interactions with mutations that cri

158 therapeutic strategy of metabolically driven synthetic lethality involving targeting glutamine metabo

159 Synthetic lethality is a genetic concept in which cell d

160 Synthetic lethality is a genetic interaction wherein two

161 Synthetic lethality is a powerful approach to study sele

162 Synthetic lethality is a state when simultaneous loss of

163 Synthetic lethality is an approach to study selective ce

164 Synthetic lethality is an innovative framework for disco

165 Synthetic lethality is associated with high levels of ap

166 In order to combat this phenomenon, synthetic lethality is being investigated, making use of

167 Genetic suppression revealed that this synthetic lethality is in part due to low expression of

168 We provide evidence that this synthetic lethality is independent of MRN cell cycle che

169 Synthetic lethality is inviability of a double-mutant co

170 Although synthetic lethality is not a new idea, recent advances,

171 bility to utilize different nutrients, while synthetic lethality is significantly less conserved.

172 Accordingly, this synthetic lethality is suppressed by increasing RRM2 exp

173 We show that this synthetic lethality is the result of defective crossover

174 tion, fulfilling the classical definition of synthetic lethality; loss of p53, SGK2, or PAK3 alone ha

175 The synthetic lethality map parallels observations made in y

176 f the mSWI/SNF complex, we propose that such synthetic lethality may be explained by paralog insuffic

177 This synthetic lethality may eventually be exploited to impro

178 Rational therapeutic approaches based on synthetic lethality may improve cancer management.

179 to bolster our understanding of fundamental synthetic lethality mechanisms and advance these finding

180 ic interactions in human cells, we created a synthetic lethality network focused on the secretory pat

181 results presented here, including extensive synthetic lethality observed between slx5delta and slx8d

182 Together, our data explain the synthetic lethality observed between topoisomerase-induc

183 an important mechanistic contributor to the synthetic lethality observed.

184 Synthetic lethality occurs when the inhibition of two ge

185 Synthetic lethalities of caf1Delta, but not that of ccr4

186 Synthetic lethality of APC/C inhibition and cohesion def

187 Synthetic lethality of asp1Delta with Ppn1, Swd22, and S

188 HDR in this background, loss of ATM leads to synthetic lethality of Brca1(S1598F) mice.

189 We found that the synthetic lethality of cells lacking both Rqh1 and Eme1

190 The findings unveil the synthetic lethality of combined suppression of YAP and R

191 Synthetic lethality of double-alanine mutations highligh

192 aploid Saccharomyces cerevisiae, we observed synthetic lethality of pol2-4 with alleles that complete

193 Accordingly, synthetic lethality of PopZ and TipN is caused by severe

194 in is not dependent on DNA damage, since the synthetic lethality of smc6 hypomorphs with a topoisomer

195 These results, along with the synthetic lethality of the bamDR197L DeltabamE double mu

196 hotopic breast cancer model, tumor-selective synthetic lethality of the combination of bioavailable A

197 sphatidylpropanolamine, failed to rescue the synthetic lethality of the crd1delta psd1delta cells.

198 gtr1 and pib2 mutants and also prevented the synthetic lethality of the double mutants.

199 ot helD null or lexA3, partially rescued the synthetic lethality of the double topoisomerase III/IV m

200 he administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with bre

201 Synthetic lethality offers a promising but largely unexp

202 using the keywords "RAS," "KRAS," "NSCLC," "synthetic lethality," "oncogenic driver mutations," "cli

203 sm for their antineoplastic activity, making synthetic lethality one of the most important new concep

204 t lattice assembly exhibited growth defects, synthetic lethality or both, supporting the function of

205 ose disruption in a rat8-2 background causes synthetic lethality or dramatically reduced growth.

206 t and DNA repair, creating opportunities for synthetic lethality or synergistic cytotoxicity.

207 In a novel synthetic lethality paradigm, we found that simultaneous

208 rspective highlights exciting targets within synthetic lethality, (PARP, ATR, ATM, DNA-PKcs, WEE1, CD

209 TPL2 knockdown and TNFalpha gives rise to a synthetic lethality phenotype via receptor-interacting s

210 This synthetic-lethality phenotype was as pronounced as that

211 DprE1, killing also occurs through chemical synthetic lethality, presumably through the lack of deca

212 Global analysis of synthetic lethality promises to identify cellular pathwa

213 Synthetic lethality provides a potential mechanistic fra

214 ic screening based on the genetic concept of synthetic lethality provides an avenue to discover drug

215 In addition to the known cdc7-rad53 synthetic lethality, rad53 mutations suppress mcm5-bob1,

216 ower frequency of essential genes and higher synthetic lethality rate, but instead diverge more in ex

217 nce of CLB5, suggesting that the bub1/3 clb5 synthetic lethality reflected some function other than t

218 duces growth of CRPC cell lines suggesting a synthetic lethality relationship between AR-Vs and PARP,

219 er, the molecular mechanisms that drive this synthetic lethality remain unclear.

220 herapeutics that takes advantage of clinical synthetic lethality, resulting in selective tumor cell k

221 we present the results of a high-throughput synthetic lethality screen for genes that interact with

222 In this study, a respiratory synthetic lethality screen revealed a role for an evolut

223 We deployed a synthetic lethality screen to investigate if knockdown o

224 A genome-wide, conditional synthetic lethality screen was performed using the yeast

225 Using a synthetic lethality screen, we identified important regu

226 combinatorial gene-network analysis, in vivo synthetic lethality screening and chromosome engineering

227 By synthetic lethality screening, we identified a small com

228 cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-geno

229 tion of TAG arrays is to perform genome-wide synthetic lethality screens, known as synthetic lethalit

230 , the identification of GLUT1 inhibitors via synthetic lethality screens, novel engagement of the ins

231 chanisms that have thus far been unveiled by synthetic lethality screens.

232 microarray (SLAM) methods have been used for synthetic-lethality screens.

233 peutic targeting of oncogenes is to perform "synthetic lethality" screens for genes that are essentia

234 Synthetic lethality (SL) is a promising form of gene int

235 genetically interacting proteins results in synthetic lethality (SL).

236 cancers, where TLS impairment might trigger synthetic lethality (SL).

237 reased uracil incorporation in DNA and known synthetic lethalities [SL(dut) mutations].

238 olecular inhibitor BIBF 1120 (BIBF) promoted synthetic lethality specifically in cells with the loss-

239 Synthetic lethality strategies for cancer therapy exploi

240 J ligands are amenable to chemically induced synthetic lethality strategies upon association with inh

241 ic optimization, rational drug combinations, synthetic lethality strategies, novel biguanides, and th

242 matin ubiquitin pathway may, therefore, be a synthetic lethality strategy for BRCA1-deficient cancers

243 ponse caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion of another AT

244 t, combining these two mutations resulted in synthetic lethality, suggesting that Mcm2 and Mcm4 play

245 Loss of cep-1 and him-5 results in synthetic lethality that is dependent on the upstream DN

246 late DNA was investigated using an assay for synthetic lethality that provides a visual readout of ce

247 The concept of synthetic lethality (the creation of a lethal phenotype

248 This study proposes a synthetic-lethality therapy for treating cancers deficie

249 e/ATPase domain to deliver on the promise of synthetic-lethality therapy.

250 tivity to promote tumor survival and confers synthetic lethality, thereby revealing a unique therapeu

251 unexplored gene-drug associations, including synthetic lethalities to prevalent alterations in liver

252 vides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic

253 Our objective was to engender synthetic lethality to paclitaxel (PTX), the frontline t

254 PARP inhibitors exploit synthetic lethality to target DNA repair defects in here

255 ression of anaplerotic Q utilization created synthetic lethality to the cell cycle phase-specific cyt

256 ts form a computational basis for exploiting synthetic lethality to uncover cancer-specific susceptib

257 DSB repair pathways sensitized MPN cells to synthetic lethality triggered by PARP inhibitors.

258 deletion from the plastid genome results in synthetic lethality under autotrophic conditions.

259 Tethering Sli15 to Ame1/Okp1 rescued synthetic lethality upon Ctf19 depletion in a Sli15 cent

260 can produce 2 distinct biological outcomes: synthetic lethality upon significant suppression of ATR

261 adigm based on the possibility of triggering synthetic lethality using only small organic molecules (

262 Synthetic lethality was observed for these mutants when

263 oadly activated in response to A3A activity, synthetic lethality was specific to ATR signaling via Ch

264 get HRR in tumor cells, a phenomenon called "synthetic lethality" was applied, which relies on the ad

265 Ultimately, the synthetic lethality we have identified between MYC overe

266 Using a screen for synthetic lethality, we found that the V. cholerae PBP1a

267 In particular, we observed synthetic lethality when both sphingolipid and PI4P synt

268 f Gcn5-targeted histone H3 residues leads to synthetic lethality when combined with deletion of the g

269 cking the centromere binding factor Cbf1 and synthetic lethality when combined with mutations in comp

270 mage response defect of sonB1 mutants causes synthetic lethality when combined with mutations in scaA

271 t mRNA accumulation that could contribute to synthetic lethality when combined with other genetic alt

272 gets, the blockade of which showed selective synthetic lethality when combined with PI3K inhibitors.

273 hic mutations of Mre11 (Mre11(ATLD1)) led to synthetic lethality when juxtaposed with DNA-PKcs defici

274 the absence of both ShyA and ShyC results in synthetic lethality, while the absence of ShyA and ShyB

275 nits SMC3, RAD21, and STAG2 and screened for synthetic lethality with 3009 FDA-approved compounds.

276 N-tail mutants exhibited synthetic lethality with an altered centromeric DNA sequ

277 dentify putative mechanisms of resistance or synthetic lethality with antibody-mediated anti-prolifer

278 , an altered outer membrane protein profile, synthetic lethality with both surA::Cm and deltafkpA::Cm

279 pindle checkpoint genes BUB1 and BUB3 caused synthetic lethality with clb5.

280 As a consequence, STAG2 mutation confers synthetic lethality with DNA double-strand break repair

281 ARPi) prevent cancer cell growth by inducing synthetic lethality with DNA repair defects (e.g., in BR

282 established human cancer cell lines induced synthetic lethality with genotoxic chemotherapeutics, in

283 ral clinically used drugs showed significant synthetic lethality with loss or inhibition of GSTO1.

284 ge, intolerance to moderate over-expression, synthetic lethality with low Deltapsi(m) conditions, hyp

285 not essential but when deleted, it leads to synthetic lethality with many secretory mutations, defec

286 The map65-4 mutation caused synthetic lethality with map65-3 although map65-4 alone

287 uxotrophy, impaired telomeric silencing, and synthetic lethality with mutations in SPT10, a gene that

288 protein misfolding, and they do not display synthetic lethality with mutations in UPR(ER) genes, whi

289 type, sensitivity to DNA damaging agents and synthetic lethality with mutations that affect DNA metab

290 Loss of SAE1/2 enzymatic activity drives synthetic lethality with Myc.

291 dentified a cohort of proteins which display synthetic lethality with paclitaxel in non-small-cell lu

292 s sporadic EOC are profoundly susceptible to synthetic lethality with PARP inhibition, it is imperati

293 ude RFP and regulatory mechanisms that cause synthetic lethality with PARPis.

294 Synthetic lethality with reduced H(+) efflux and activat

295 NPC clustering, nuclear import defects, and synthetic lethality with the additional absence of Pom34

296 pbn1-1, a nonlethal allele of PBN1, displays synthetic lethality with the ero1-1 allele (ERO1 is requ

297 BIM1, and KAR3), and they all share the same synthetic lethality with the first group.

298 Deletion of the RPB9 gene shows synthetic lethality with the low fidelity rpb1-E1103G mu

299 n to identify genes that when silenced cause synthetic lethality with the PARP inhibitor AZD2281.

300 eens to identify genes whose depletion shows synthetic lethality with VX-680.