ライフサイエンスコーパス: TLS

1 TLS activity is an important risk factor for the initiat

2 TLS and TS depend on site-specific PCNA K164 monoubiquit

3 TLS density and GC formation were each reduced in chemot

4 TLS measurements are helping to test fundamental ecologi

5 TLS polymerases are capable of bypassing a distorted tem

6 TLS(+) tissues exhibited a significantly increased expre

7 TLSs in this model were spatially associated with >90% o

8 TLSs thus reveal an advanced level of self-organization

9 PrimPol was recently identified as a TLS primase and polymerase involved in DNA damage tolera

10 The E3 ubiquitin ligase RAD18 activates TLS by promoting recruitment of Y-family DNA polymerases

11 In addition, TLS has been implicated as a major cellular mechanism pr

12 ly involved in priming replication, are also TLS proficient and therefore may play important roles in

13 gy, and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSC

14 eal a key player in the regulation of HR and TLS with significant clinical implications.

15 rved during the development of murine LN and TLS.

16 mportant role in PCNA monoubiquitination and TLS in a FANCD2 monoubiquitination and HR-independent ma

17 ce-promoting HDR, while suppressing NHEJ and TLS.

18 We conclude that both replicative and TLS polymerases can bypass this DpC lesion in human cell

19 As with another TLS polymerase, Pol IV, increasing concentrations of Pol

20 Because TLS efficiency of the DpC construct was not significantl

21 We propose that both TLS-dependent and deamination-dependent mutational proce

22 nce the efficiency and fidelity of bypass by TLS polymerases.

23 east triggers a switch to MMBIR catalyzed by TLS polymerases.

24 capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impe

25 elanomas, was produced almost exclusively by TLS.

26 lls but that mutations are induced mainly by TLS polymerases.

27 After bypass of 8-oxoG by TLS PolY, products accumulate at the template position t

28 basic site bypass independently of canonical TLS polymerases.

29 prokaryotes and eukaryotes possess canonical TLS polymerases (Y-family Pols) capable of traversing bl

30 We show that, unlike canonical TLS polymerases, PrimPol is important for allowing activ

31 ients treated with neoadjuvant chemotherapy, TLS density was similar, but GC formation was impaired a

32 Conclusion: Clinical TLS is a rare but definite complication of RLT, suggesti

33 Rev1 polymerase and Poltheta conduct TLS opposite epsilondA via alternative error-prone pathw

34 In contrast, TLS(+) tissues contained significantly more NIK(+) ECs a

35 In contrast, loss of Rad18-dependent TLS potentiates the collapse of stalled forks and leads

36 cleotide lesions by ggNER and Rev1-dependent TLS, respectively.

37 cycles) were screened; 4 patients developed TLS with clinical symptoms and characteristic changes in

38 ice, establishing a framework for developing TLS inhibitors as a novel class of chemotherapy adjuvant

39 Whereas different TLS groupings yielded similar Bragg intensities, they yi

40 indicated that mRNAs harboring a distinctive TLS can move from transgenic roots into wild-type leaves

41 r low fidelity of synthesis opposite 3-dMeA, TLS opposite this lesion replicates DNA in a highly erro

42 cells can, at different times, modulate DNA TLS for improved cell survival.

43 n DNA generates extensive frameshifts during TLS, which can lead to genomic instability.

44 ing to the lymphatic vascular network during TLS development have not been studied.

45 t and passive exchange of polymerases during TLS on the lagging strand.

46 yeast, POLD3 is required for fully effective TLS, its loss resulting in hypersensitivity to a variety

47 lational modification required for efficient TLS activation.

48 talytic activity, was required for efficient TLS.

49 e binding of pol eta to PCNA and the ensuing TLS are both independent of PCNA ubiquitination.

50 amages in a hydrophobic pocket to facilitate TLS.

51 polymerase eta (Pol eta) and other Y-family TLS polymerases to damaged DNA relies on proliferating c

52 x642 and BTx623/SC155-14E, were assessed for TLS resistance in replicated trials.

53 spectively screened our patient database for TLS after RLT in neuroendocrine tumors and prostate canc

54 they display remarkably low efficiencies for TLS compared to normal DNA synthesis.

55 tin-conjugating enzyme RAD6 is essential for TLS.

56 gs that these residues are indispensable for TLS by the purified Pol but are not required in human ce

57 ts and showed that Rev1 is indispensable for TLS mediated by Poleta, Poliota, and Polkappa but is not

58 ise, or consecutive, thermodynamic model for TLS folding is developed, which is in good agreement wit

59 RLT, suggesting that patient monitoring for TLS should be mandatory.

60 s the implications of these observations for TLS mechanisms in human cells.

61 oliota, and Polkappa but is not required for TLS by Polzeta.

62 therapy; and by reducing mutation formation, TLS inhibition may dampen the emergence of drug-resistan

63 Using least square mean trait data, four TLS resistance QTL were identified, two in each populati

64 zed the relative contributions of error-free TLS by Poleta and error-prone TLS by Poltheta to the rep

65 ltheta, it performs predominantly error-free TLS in human cells.

66 , Poltheta performs predominantly error-free TLS in human cells.

67 vide Poltheta the proficiency for error-free TLS in human cells.

68 east, Rev1 promotes predominantly error-free TLS opposite UV lesions in humans.

69 Whereas TS is mainly error-free, TLS can work in an error-prone manner and, as such, the

70 We derive an allometry from TLS that spans a much greater range of tree size than pr

71 etal-ion dependent formation of a functional TLS domain from unfolded RNAs via two consecutive steps:

72 Furthermore, TLS affords human cancer cells the ability to counteract

73 Furthermore, TLS density correlated with GC formation and expression

74 of specific ASO-binding proteins such as FUS/TLS (FUS) and PSF/SFPQ (PSF).

75 in sarcoma/translocated in liposarcoma (FUS/TLS or FUS).

76 Mutations in the RNA-binding protein FUS/TLS (FUS) have been linked to the neurodegenerative dise

77 However, little is known about how TLS develop in cancer, how their function affects surviv

78 called translesion synthesis (TLS), but how TLS polymerases gain access to the DNA template remains

79 elegans and zebrafish embryos, and show how TLS-SPIM can facilitate cell biology research in multice

80 However TLS-derived AGB was more than 30% higher compared to wid

81 Is in DDR pathways (BER, MMR, NER, NHEJ, HR, TLS, and ICL repair) are specifically discussed for inhi

82 Human TLS involves the conjugation of ubiquitin to PCNA clamps

83 Human TLS requires selective monoubiquitination of proliferati

84 on corresponded to the previously identified TLS resistance gene ds1.

85 ients, so we evaluated whether they impaired TLS development independently of chemotherapy.

86 construct was not significantly affected in TLS polymerase-deficient cells, we examined a possible r

87 e POLD3 subunit of Poldelta are deficient in TLS.

88 very low numbers, but not differentially in TLS(+) tissues.

89 highlight the importance of GC formation in TLS during tumor development and treatment.Significance:

90 ta, Poliota, and Polkappa, which function in TLS in highly specialized ways opposite a diverse array

91 cialized DNA repair polymerase, functions in TLS and allows for DNA replication complexes to bypass l

92 However, how Rev1 functions in TLS and mutagenesis in human cells has remained unclear.

93 Despite its importance in TLS, the structure of Polzeta is unknown.

94 rgeting the LTalpha1beta2/LTbetaR pathway in TLS-associated pathologies might impair a natural prores

95 unctional requirements of this population in TLS development are unclear.

96 Here we determined the role of Rev1 in TLS opposite UV lesions in human and mouse fibroblasts a

97 molecular underpinnings of Polzeta's role in TLS and provide a framework for new cancer therapeutics.

98 and suggesting novel therapeutic targets in TLS-associated diseases.

99 riation in the MAMP response to variation in TLS resistance.

100 provides the proof-of-concept of inhibiting TLS as a therapeutic approach to selectively kill HR-def

101 leading strand upon uncoupling and inhibits TLS.

102 In conclusion, kidney TLS have a similar cell composition, structure, and gene

103 Tbx6 knockout TLSs developed additional neural tubes mirroring the emb

104 d not differ between schedules (2 laboratory TLSs per schedule).

105 ed between stronger flg22 response and lower TLS resistance.

106 (LSCC) and in an experimental model of lung TLS induction.

107 confirmed in the experimental model of lung TLS induction.

108 es isolated from lymph nodes, macrodissected TLS from kidneys, and total kidneys of mice at different

109 one at inserting nucleotides opposite 1-MeA, TLS opposite this lesion in human cells occurs in a high

110 ion of DNA polymerase complexes that mediate TLS and describe how this knowledge is beginning to tran

111 have intrinsically enhanced Pol eta-mediated TLS, allowing CSCs to survive cisplatin treatment, leadi

112 as monoubiquitination by Rad6/Rad18 mediates TLS, extension of this ubiquitin to a polyubiquitin chai

113 eet selective plane illumination microscopy (TLS-SPIM) with real-time light-sheet optimization was de

114 fusing RNA constructs resembling the minimal TLS element of brome mosaic virus RNA3.

115 slate into the development of small molecule TLS inhibitors.

116 inhibitor, JH-RE-06, that disrupts mutagenic TLS by preventing recruitment of mutagenic POL zeta.

117 ecificity and in vivo efficacy for mutagenic TLS has been challenging.

118 In contrast to its role in mutagenic TLS in yeast, Rev1 promotes predominantly error-free TLS

119 JH-RE-06 inhibits mutagenic TLS and enhances cisplatin-induced toxicity in cultured

120 e UV lesions would generate these mutations, TLS mechanisms are presumed to underlie cancer developme

121 than the wild type enzyme, with over 90% of TLS events resulting in dA incorporation.

122 e demonstrate the 3D live imaging ability of TLS-SPIM by imaging cellular and subcellular behaviours

123 However, the access of TLS polymerases to the replication machinery must be kep

124 ic RAD18-binding partner and an activator of TLS.

125 Current and future applications of TLS V.

126 ntroduces the background and capabilities of TLS in forest ecology, discusses some of the barriers to

127 However, the efficiency of TLS activity decreases with increase in the steric bulki

128 Failure of TLS polymerases to overcome this barrier leads to reprim

129 ibition mechanism is an intrinsic feature of TLS-mediated lesion bypass functioning to curtail the in

130 This suggests that the in vivo fidelity of TLS Pols is regulated by factors such as post-translatio

131 Formation of TLS was found in anti-double-stranded DNA antibody-posit

132 X, thereby recapitulating major hallmarks of TLS deficiency.

133 Thus, the inhibition of TLS becomes a promising point of therapeutic interventio

134 k of selective pharmacological inhibitors of TLS.

135 The length of TLS must be long enough for effective bypass, but it mus

136 D2 monoubiquitinations (surrogate markers of TLS and FA pathway activation, respectively) and with at

137 ith Rev1 mediates a highly mutagenic mode of TLS.

138 Using a viral-induced, resolving model of TLS formation in the salivary glands of adult mice we de

139 The error-prone nature of TLS may provide mechanistic understanding of the accumul

140 t are able to support the earliest phases of TLS establishment.

141 ent AKT inhibition blocks the recruitment of TLS polymerases to sites of DNA damage and impairs DNA r

142 tment to the chromatin and the regulation of TLS.

143 The prominent role of TLS in promoting proficient and mutagenic replication th

144 To address the role of TLS in skin cancer formation, we determined which DNA po

145 (4)-alkyldT lesions and defined the roles of TLS polymerases in bypassing these lesions in human cell

146 h nodes revealed a similar gene signature of TLS and lymph nodes.

147 We also characterized sequential stages of TLS maturation in LSCC culminating in the formation of g

148 ut both the insertion and extension steps of TLS opposite 3-dMeA, and in the Polzeta pathway, Polzeta

149 nucleotide insertion and extension steps of TLS, and in the third pathway, Polzeta would extend from

150 oratory or clinical abnormalities typical of TLS within 7 d after the start of treatment.

151 rocess, provide our current understanding of TLS on leading and lagging strand templates, and propose

152 ion was impaired and the prognostic value of TLS density was lost.

153 cing BAFF in vivo prevented the formation of TLSs and lupus nephritis; however, it did not reduce imm

154 ment but also contribute to the formation of TLSs in chronic inflammation.

155 n NIK(+) ECs, (pre)FDCs, and the presence of TLSs, indicating that NIK(+) ECs may not only be importa

156 UV irradiation does not exclusively rely on TLS events.

157 ry of DDT in the late 1960s, most studies on TLS in eukaryotes have focused on DNA lesions resulting

158 We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and d

159 Our TLS estimates agree to within 2% AGB with a species-spec

160 with the T residue, Poliota would carry out TLS opposite 1-MeA, the ability of Poleta to replicate t

161 In untreated patients, TLS density was the strongest independent prognostic mar

162 i S, primase small subunit) can also perform TLS.

163 of a high-fidelity DNA polymerase to perform TLS with 8-oxo-guanine (8-oxo-G), a highly pro-mutagenic

164 deficient human Poldelta holoenzyme performs TLS of abasic sites in vitro much more efficiently than

165 We suggest that where possible, TLS and crown mapping should be used to provide compleme

166 accumulate in late S and G2 when productive TLS is critical for cell survival.

167 We found that Pol nu and Pol theta promote TLS across major-groove O (6)-alkyl-dG lesions.

168 mice support the conclusion that error-prone TLS by Poltheta provides a safeguard against tumorigenes

169 of error-free TLS by Poleta and error-prone TLS by Poltheta to the replication of UV-damaged DNA and

170 ly carry out the majority of the error-prone TLS of dG-C8-IQ, whereas pol eta is involved primarily i

171 kingly, in contrast to extremely error-prone TLS opposite epsilondA by purified Poltheta, it performs

172 Consistent with the role of RAD6/TLS in late-S phase, SMI#9-induced DNA replication inhib

173 deepen insights into the vital role of RAD6/TLS in platinum drug tolerance and reveal clinical benef

174 el purports that ubiquitinated PCNA recruits TLS polymerases such as pol eta to sites of DNA damage w

175 s-prone mice during LN development reflected TLS formation, whereas the down-regulated genes were inv

176 igen monoubiquitination positively regulates TLS to overcome Pol delta inhibition.

177 Renal TLS was characterized in lupus-prone New Zealand black x

178 ison of gene profiles of whole kidney, renal TLS, and lymph nodes revealed a similar gene signature o

179 ed role in lupus nephritis by inducing renal TLSs and regulating the position of T cells within the g

180 n ICL, its bypass may not absolutely require TLS polymerases.

181 nome replication in vivo and, when required, TLS of abasic sites.

182 This significantly restored TLS in pold3 mutants, enhancing dA incorporation opposit

183 irst detailed 3D terrestrial laser scanning (TLS) estimates of the volume and AGB of large coastal re

184 erences SUMMARY: Terrestrial laser scanning (TLS) is providing new, very detailed three-dimensional (

185 ment, we tested translation-libration-screw (TLS), liquid-like motions (LLM), and coarse-grained norm

186 was able to successfully perform abasic site TLS without template realignment and inserting preferabl

187 sion synthesis (TLS), in which a specialized TLS Pol is recruited and replaces the stalled HiFi Pol f

188 Rev1 is a specialized TLS polymerase that bypasses abasic sites, as well as mi

189 thesis (TLS) during S-phase uses specialized TLS DNA polymerases to replicate a DNA lesion, allowing

190 lso assessed resistance to Target Leaf Spot (TLS) disease caused by the necrotrophic fungus Bipolaris

191 Target leaf spot (TLS) of sorghum, a foliar disease caused by the necrotro

192 -studied systems is the tRNA-like structure (TLS) domain, which has been found to occur in many plant

193 associated with tertiary lymphoid structure (TLS) has been reported in numerous studies.

194 s organized as tertiary lymphoid structures (TLS) are observed within the kidneys of patients with sy

195 uctures called tertiary lymphoid structures (TLS) is associated with improved patient survival.

196 gregation into tertiary lymphoid structures (TLS).

197 ly associating domain (TAD)-like structures (TLSs) can be identified within single cells, and their c

198 transcripts harboring tRNA-like structures (TLSs) that were found to be enriched in the phloem strea

199 ation of renal tertiary lymphoid structures (TLSs).

200 of highly organized "trunk-like structures" (TLSs) comprising the neural tube and somites.

201 (+) and PD-L1(+) epithelial cells supporting TLS formation.

202 onal role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel thera

203 and the occurrence of tumor lysis syndrome (TLS) with (177)Lu-labeled peptides has not yet been repo

204 including incidence of tumor lysis syndrome (TLS), did not differ between schedules (2 laboratory TLS

205 es specialized in translesion DNA synthesis (TLS) aid DNA replication.

206 Translesion DNA synthesis (TLS) and homologous recombination (HR) cooperate during

207 Translesion DNA synthesis (TLS) during S-phase uses specialized TLS DNA polymerases

208 mutations of the translesion DNA synthesis (TLS) gene REV7 (also known as MAD2L2), which encodes the

209 Translesion DNA synthesis (TLS) is the ability of DNA polymerases to incorporate nu

210 plate strand, and translesion DNA synthesis (TLS) is used to rescue progression of stalled replisomes

211 Translesion DNA synthesis (TLS) mediated by low-fidelity DNA polymerases is an esse

212 he lower-fidelity translesion DNA synthesis (TLS) polymerase Poleta is proficient, inserting both cor

213 th an appropriate translesion DNA synthesis (TLS) polymerase, followed by PCR amplification and next-

214 using appropriate translesion DNA synthesis (TLS) polymerases and then can be amplified by PCR.

215 on fork reversal, translesion DNA synthesis (TLS), and repriming.

216 In translesion DNA synthesis (TLS), specialized DNA polymerases replicate the damaged

217 nsion reaction in translesion DNA synthesis (TLS).

218 be carried out by translesion DNA synthesis (TLS).

219 gase Rad18 activates Trans-Lesion Synthesis (TLS) and the Fanconi Anemia (FA) pathway.

220 Trans-lesion synthesis (TLS) is an important DNA-damage tolerance mechanism that

221 ase, demonstrate that translesion synthesis (TLS) across these N(2)-dG adducts is error free.

222 distinct mechanisms: translesion synthesis (TLS) and template switching (TS)-dependent pathways.

223 ts additional role in translesion synthesis (TLS) as a subunit of DNA polymerase zeta.

224 One process is translesion synthesis (TLS) by DNA polymerases (Pol) delta, eta and zeta, which

225 ract REV7 function in translesion synthesis (TLS) by releasing it from REV3 in the Pol zeta complex.

226 sembles the REV7-REV3 translesion synthesis (TLS) complex, a component of the Fanconi anaemia pathway

227 Because mutagenic translesion synthesis (TLS) contributes to chemoresistance as well as treatment

228 ncorporated into DNA, translesion synthesis (TLS) DNA Pols could reduce the effectiveness of AraC in

229 es of replicative and translesion synthesis (TLS) DNA polymerases (Pols) are retained in their cellul

230 Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through

231 The roles of translesion synthesis (TLS) DNA polymerases in bypassing the C8-2'-deoxyguanosi

232 ells where individual translesion synthesis (TLS) DNA polymerases were depleted by the CRISPR/Cas9 ge

233 However, translesion synthesis (TLS) DNA polymerases, such as Rev1, have the ability to

234 t observed when other translesion synthesis (TLS) DNA polymerases-hpol iota, kappa, or zeta-were indi

235 a set of low-fidelity translesion synthesis (TLS) DNA polymerases.

236 In contrast, translesion synthesis (TLS) DNAPs are suitable for replicating modified templat

237 comparatively studied translesion synthesis (TLS) efficiency and mutagenesis of the DpC in a series o

238 Translesion synthesis (TLS) employs specialized DNA polymerases to bypass repli

239 ) nu and Pol theta in translesion synthesis (TLS) in cells.

240 DNA translesion synthesis (TLS) is a crucial damage tolerance pathway that oversees

241 ), a component of the translesion synthesis (TLS) machinery, could potentiate the action of cisplatin

242 to promote error-free translesion synthesis (TLS) mediated by DNA polymerase eta (Poleta).

243 Here we show that translesion synthesis (TLS) opposite 1,N(6)-ethenodeoxyadenosine (epsilondA), w

244 s incorporated during translesion synthesis (TLS) opposite UV lesions would generate these mutations,

245 eta and Rev1 to study translesion synthesis (TLS) past a nitrogen mustard-based interstrand crosslink

246 everal members of the translesion synthesis (TLS) pathway, a DNA damage tolerance pathway, and that t

247 analyzed the roles of translesion synthesis (TLS) Pols in the replication of 3-MeA-damaged DNA in hum

248 n fork, including the translesion synthesis (TLS) polymerase poleta.

249 MMBIR, are driven by translesion synthesis (TLS) polymerases Polzeta and Rev1.

250 itment of specialized translesion synthesis (TLS) polymerases that have evolved to incorporate nucleo

251 to restrict access of translesion synthesis (TLS) polymerases to the primer/template junction.

252 In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multif

253 f the unhooked ICL by translesion synthesis (TLS) polymerases.

254 a-dependent mutagenic translesion synthesis (TLS) promotes cell survival after DNA damage but is resp

255 age, a process called translesion synthesis (TLS) that alleviates replication stalling.

256 nt with activation of translesion synthesis (TLS) under these conditions, SAHA and cisplatin cotreatm

257 s in a process called translesion synthesis (TLS), but how TLS polymerases gain access to the DNA tem

258 ncerted activities of translesion synthesis (TLS), Fanconi anemia (FA), and homologous recombination

259 involves 'on-the-fly' translesion synthesis (TLS), in which a specialized TLS Pol is recruited and re

260 sine (1,N (6)-erA) on translesion synthesis (TLS), mediated by human DNA polymerase eta (hpol eta), a

261 have been documented: translesion synthesis (TLS), template switching (TS), and repriming.

262 a core factor in DNA translesion synthesis (TLS), the postreplicative bypass of damaged nucleotides.

263 genomes by promoting translesion synthesis (TLS), this comes at a cost of potentially error-prone le

264 we have reconstituted translesion synthesis (TLS)-mediated restart of a eukaryotic replisome followin

265 s believed to inhibit translesion synthesis (TLS).

266 tunnel barrier with fewer two-level system (TLS) defects, and secondarily to fabricating the devices

267 TA-TLSs have been described in human lung cancers, but thei

268 Thus, we propose that Treg cells in TA-TLSs can inhibit endogenous immune responses against tum

269 d T cell proliferation rates increased in TA-TLSs upon Treg cell depletion, leading to tumor destruct

270 -associated tertiary lymphoid structures (TA-TLSs).

271 ll as treatment-induced mutations, targeting TLS is an attractive avenue for improving chemotherapeut

272 , Poliota, and Polnu, respectively; and that TLS by all these Pols incurs considerable mutagenesis.

273 to the replication of AraC-damaged DNA; that TLS through AraC is conducted by three different pathway

274 We provide evidence that TLS makes a consequential contribution to the replicatio

275 We find that TLS functions 'on the fly' to promote resumption of rapi

276 The information that TLS measurements can provide in describing detailed, acc

277 nature of DNA replication, it is likely that TLS on the leading and lagging strand templates is uniqu

278 genic replication through AraC suggests that TLS inhibition in acute myeloid leukemia patients would

279 Interestingly, Rad51 and the TLS polymerase poleta modulate the elongation of nascent

280 ulated to minimize replication errors by the TLS Pol.

281 Here we identify the TLS Pols required for replicating through the AraC templ

282 lts presented here provide insights into the TLS across N(2)-aryl-dG damaged DNAs by Pol IV.

283 the HiFi Pol resumes (i.e. the length of the TLS patch) has not been described.

284 survival after DNA damage, inhibition of the TLS pathway has emerged as a potential target for the de

285 reover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and d

286 tant, unrestrained replication relies on the TLS protein REV1.

287 ings establish that PolDIP2 can regulate the TLS polymerase and primer extension activities of PrimPo

288 The exact position where the TLS Pol ends and the HiFi Pol resumes (i.e. the length o

289 efined against the diffuse data, whereas the TLS and NM models provide more detailed and distinct des

290 nockdown of hPol zeta, suggesting that these TLS polymerases play a critical role in error-prone DpC

291 These data support Poldelta contributing to TLS in vivo and suggest that the mutagenesis resulting f

292 at POLD3 makes a significant contribution to TLS independently of Polzeta in DT40 cells.

293 We further show that translesion (TLS) polymerase PolH chromatin localization is decreased

294 ->A mutations that were modulated by the two TLS polymerases and the structures of the alkyl groups.

295 In vitro TLS using yeast pol zeta showed that it can extend G3*:A

296 thway unfolds, in particular, where and when TLS occurs on each template strand.

297 intervention in HR-deficient cancers, where TLS impairment might trigger synthetic lethality (SL).

298 ermediate indicates a defined position where TLS Pol extension is limited and where the DNA substrate

299 o repriming, which competes kinetically with TLS.

300 is of the DpC in a series of cell lines with TLS polymerase knockouts or knockdowns.