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1 ICL confers an increased risk of opportunistic infection
2 ICL predisposes patients to severe opportunistic infecti
3 ICL repair requires unhooking of the tethered strands by
4 ICL-1 utilizes a bioinspired endoperoxide trigger to rel
5 ICL-labeled cells disappeared from blood almost immediat
6 ICLs are produced upon irradiation under anoxic conditio
7 ICLs are thought to be processed by proteins from a vari
8 characterization of iron-caged luciferin-1 (ICL-1), a bioluminescent probe that enables longitudinal
9 emain unclear.METHODSWe hybridized 34 and 51 ICL patients' sera to a 9,000-human-proteome array and t
12 e angle narrowing was detected 1 month after ICL V4c implant, this narrowing remained stable at 3 mon
17 cterized Escherichia coli protein YcaQ as an ICL repair glycosylase that protects cells against the t
19 tivated when a replication fork stalls at an ICL(2); this triggers monoubiquitination of the ID compl
20 t NEIL3 to replication forks converged at an ICL, but the nature of DNA binding and the effect of the
23 the structure and extent of processing of an ICL, its bypass may not absolutely require TLS polymeras
25 When a replication fork collides with an ICL, it triggers a damage response that promotes multipl
27 pathways (BER, MMR, NER, NHEJ, HR, TLS, and ICL repair) are specifically discussed for inhibitor dis
28 umulation of CSB at sites of monoadducts and ICLs, but it did not affect recruitment to (although sli
30 hooks both sides of symmetric and asymmetric ICLs in vitro, and loss or overexpression of ycaQ sensit
33 te can unhook either or both sides of an AZB ICL, providing a basis for understanding the mechanisms
36 siae, a vestigial FA pathway is present, but ICLs are predominantly repaired by a pathway involving t
37 FANCD2 proteins that subsequently coordinate ICL removal and repair of the ensuing DNA double-strande
38 acts, we describe here a replication-coupled ICL repair pathway that does not require incisions or FA
42 plication-coupled DNA interstrand crosslink (ICL) repair, the XPF-ERCC1 endonuclease is required for
46 itrogen mustard-based interstrand crosslink (ICL) with an 8-atom linker between the crosslinked bases
49 been shown to unhook interstrand crosslinks (ICL) in Xenopus extracts, how NEIL3 participants in ICL
50 or the repair of DNA interstrand crosslinks (ICL), a highly toxic lesion that leads to chromosomal in
54 in the repair of DNA interstrand crosslinks (ICLs) and regulates cellular responses to replication st
55 in the repair of DNA interstrand crosslinks (ICLs) are associated with the genome instability syndrom
59 umor agents form DNA interstrand crosslinks (ICLs), but their clinical efficiency is counteracted by
60 osslinks, especially interstrand crosslinks (ICLs), cause cytotoxicity via blocking replication and t
61 emotherapy cause DNA interstrand crosslinks (ICLs), which covalently link both strands of the double
65 optical cavity operating with a 3.29 mum cw ICL is detailed, and a quantitative characterization of
66 gher accumulation of the extremely cytotoxic ICLs and DSBs lesions, which in turn triggers the induct
67 ted benzyl cations alkylated dG, dC, and dA, ICL assay with variation of DNA sequences showed that th
69 s (KIN), but it is unclear whether defective ICL repair is responsible or whether Fan1 nuclease activ
70 ng, differentiated state, as well as delayed ICL processing as revealed by a modified Comet assay and
71 D2, and Merit40-null cells exhibited delayed ICL unhooking coupled with reduced end resection and hom
72 cted T-lymphocyte cell line Jurkat delivered ICLs to the BM more efficiently than erythrocytes, and m
73 i and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosi
74 ike DNA glycosylases unhook psoralen-derived ICLs in various DNA structures via a genuine repair mech
77 Interestingly, Merit40 mutation exacerbated ICL-induced chromosome instability in the context of con
78 ycosylase that protects its host by excising ICLs derived from azinomycin B (AZB), a potent antimicro
80 roteins act in a linear hierarchy: following ICL detection on chromatin, the FA core complex monoubiq
83 al of 107 eyes from 56 patients assessed for ICL implantation at our institution were included in the
88 Monoubiquitination of ID is essential for ICL repair by excision, translesion synthesis and homolo
89 rug Administration's accepted guidelines for ICL sizing, clinicians should be aware of and account fo
92 (FA) pathway is the principal mechanism for ICL repair in metazoans and is coupled to DNA replicatio
93 itinated ID complex loses its preference for ICL and related branched DNA structures, and becomes a s
96 mice, we show that Trp53 is responsible for ICL-induced bone marrow failure and that loss of Trp53 i
97 myopic subjects consecutively scheduled for ICL implant, FDOCT (RTVue; Optovue Inc) iridocorneal ang
98 ibose (dR) and one dR groups will screen for ICLs as modified dinucleosides; the accurate mass neutra
100 aster cross-linking reaction rate and higher ICL efficiency than the corresponding 2-nitro analogues.
103 that a high prevalence of autoantibodies in ICL, some of which are specific for CD4+ T cells, may co
109 rovide insight into the mechanism of FAN1 in ICL repair and demonstrate that the Fan1 mouse model eff
110 We also establish that PTEN function in ICL repair is dependent on its protein phosphatase activ
111 nucleases, and the DOG-1 (FANCJ) helicase in ICL resolution, influenced by the replicative-status of
115 Xenopus extracts, how NEIL3 participants in ICL repair in human cells and its corporation with the c
116 ceptor (TCR) signaling have been reported in ICL, but the mechanistic and causative links remain uncl
117 Cdc48/VCP segregase plays a critical role in ICL repair by unloading the CMG complex from chromatin.
120 gs identify a premature T-cell senescence in ICL that might be caused by chronic T-cell activation an
123 in human cells, and its depletion increases ICL-induced mutagenesis in human cells without altering
124 cover replication-dependent and -independent ICL repair networks, and establish nematodes as a model
125 advance our understanding of FA-independent ICL repair and establish a role for the RecQ4 helicases
126 f BRCA1, NUMB, or HES1 or chemically induced ICL damage in primary murine luminal MECs results in per
127 be recruited to localized trioxsalen-induced ICL damage in human cells, with accumulation being suppr
129 abolish interaction with RFWD3 also inhibit ICL repair, demonstrating that RPA-mediated RFWD3 recrui
130 The heat stability study of the isolated ICL products indicated that dGs were the preferred alkyl
132 using mid-infrared interband cascade lasers (ICLs) is a sensitive technique for trace gas sensing.
133 e.g., Cu(3) Sn) intermetallic coating layer (ICL) is rationally designed to stabilize Sn through a st
134 after 2 years of implantable collamer lens (ICL) V4c (STAAR Surgical AG, Nidau, Switzerland) placeme
135 Importance: Intraocular collamer lenses (ICLs) are posterior chamber phakic lenses that provide a
136 substrate containing a nitrogen mustard-like ICL two nucleotides in the duplex region because FAN1, u
139 is required for DNA interstrand cross-link (ICL) repair and is thus central to the maintenance of ge
140 uring eukaryotic DNA interstrand cross-link (ICL) repair, cross-links are resolved ("unhooked") by nu
143 y lethal lesion are interstrand cross-links (ICL), a property exploited by several anti-cancer chemot
144 ooking highly toxic interstrand cross-links (ICLs) and bulky minor groove adducts normally recognized
153 ity to generate DNA interstrand cross-links (ICLs), which effectively block the progression of transc
157 very of fluorescent indocarbocyanine lipids (ICLs, DiR, DiD, DiI) as a model lipophilic cargo, via di
158 interaction profile near intracellular loop (ICL) 2/TM3 at the G-protein-coupling interface, suggesti
159 epducin for the beta2AR, intracellular loop (ICL)1-9, was used to decouple beta-arrestin-biased signa
162 e of the glyoxylate shunt, isocitrate lyase (ICL), may mediate survival of Mtb during the acute and c
164 Idiopathic CD4+ T cell lymphocytopenia (ICL) is a heterogeneous syndrome presenting with persist
171 78 patients undergoing consecutive V4 model ICL implantations, which took place from January 1, 1998
172 enses implanted were as follows: 53 V4 model ICLs of -15.5 D or greater, 73 V4 model ICLs of less tha
173 odel ICLs of -15.5 D or greater, 73 V4 model ICLs of less than -15.5 diopter (D), and 7 V4 model tori
174 d a panel of model unhooked nitrogen mustard ICLs to systematically investigate how the state of an u
180 oxylate levels using a chemical inhibitor of ICL restored growth of MS-deficient Mtb, despite inhibit
184 ir potential contribution to pathogenesis of ICL remain unclear.METHODSWe hybridized 34 and 51 ICL pa
188 of NER and DSB/R (P <0022), similar rates of ICL/R, and more condensed chromatin structure compared w
189 rates of NER and DSB/R, comparable rates of ICL/R, more condensed chromatin structure, and higher se
192 o report that unloading of RPA from sites of ICL induction is perturbed in RFWD3-deficient cells.
194 implicate MERIT40 in the earliest stages of ICL repair and define specific functional interactions b
195 shown to be necessary in the early steps of ICL repair to prevent aberrant nuclease resection, the r
196 pathways; however, a clear understanding of ICL recognition and repair processing in human cells is
199 ors that protect against the genotoxicity of ICLs generated by trioxsalen/ultraviolet A (TMP/UVA) dur
203 ecruitment, CSA itself localized at sites of ICLs, DSBs and monoadducts but not at oxidative lesions.
205 d disease; it also brings a renewed focus on ICL that will likely result in improved diagnostic evalu
206 ation of the classical complement pathway on ICL CD4+ T cells.RESULTSAll ICL patients had a multitude
207 , HMGB1 functions in association with XPA on ICLs and facilitates the formation of a favorable archit
208 vault height (distance between the posterior ICL surface and anterior lens surface) measured a mean (
210 in principle explain how Ub-Fancd2 promotes ICL repair, but we show that recruitment of Fan1 by Ub-F
211 ) protein bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro, cooperatively with NER damage
212 with both NEIL3 and FA pathways in psoralen-ICL repair, suggesting that TRAIP may function upstream
215 hway is the major pathway to repair psoralen-ICL through a unique DSB-free mechanism in human cells.
216 is the major pathway for repairing psoralen-ICL, and the FA/BRCA pathway is only activated when NEIL
218 ortantly, the NEIL3 pathway repairs psoralen-ICLs without generating double-strand breaks (DSBs), unl
221 epair (NER), interstrand cross-links repair (ICL/R), double-strand breaks repair (DSB/R), and chromat
222 TbSNM1, a nuclease that specifically repairs ICLs, are hypersensitive to most ABQ prodrugs, a phenoty
223 ement pathway on ICL CD4+ T cells.RESULTSAll ICL patients had a multitude of autoantibodies mostly di
225 activity, caused by elongation of the short ICL-unhooked oligonucleotide (a six-mer in our study) by
226 itro from Jurkat cells resulted in a similar ICL delivery as the injection of intact Jurkat cells.
227 that while purified XPF-ERCC1 incises simple ICL-containing model replication fork structures, the pr
230 a result, the Sn anode enhanced by the Cu-Sn ICL shows a significant improvement in cycling stability
231 tion of the metallic Cu phase from the Cu-Sn ICL, which provides a regulatable and appropriate distri
232 on nuclease activity through a site-specific ICL in vitro We noted that stimulation of Pso2 nuclease
234 fore, NBD2 might be critical for stabilizing ICLs 2 and 3 that form a tetrahelix bundle at the NBD2 i
237 f success as large as 0.25 +/- 0.22 in the T-ICL group and 0.24 +/- 0.15 in the T-Artiflex group.
238 safety index was mean 1.40 +/- 0.70 in the T-ICL group and 1.20 +/- 0.21 in the T-Artiflex group.
240 study compared 82 eyes of 41 patients with T-ICL lenses in one eye and toric Artiflex implantation in
241 bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro, cooperatively with NER damage recognitio
243 re, we demonstrate that HMGB1 recognizes TFO-ICLs in human cells, and its depletion increases ICL-ind
244 ospective single center study indicates that ICL implantation provides good long-term safety and stab
246 focal microscopy of intact BM confirmed that ICLs are delivered independently of the injected cells.
249 icient human cells significantly altered the ICL-induced mutation spectrum from predominantly T-->A t
250 alone showed a tendency to stall before the ICL, whereas Pol eta stalled just after insertion across
254 n fatty acids accumulated high levels of the ICL aldehyde endproduct, glyoxylate, and increased level
255 l of these pathways require unhooking of the ICL from one strand of a DNA duplex by nucleases, follow
257 versal, are not an integral component of the ICL repair, pointing to a different mechanism of fork pr
259 The stalling of Pol eta directly past the ICL is attributed to its autoinhibitory activity, caused
260 stalling by Rev1-Pol zeta directly past the ICL was observed, suggesting that the proposed function
261 ing strand of a replication fork strikes the ICL Here, we report that while purified XPF-ERCC1 incise
262 h variation of DNA sequences showed that the ICL reaction occurred with opposing dG/dC but not with s
263 rticle particle formation was not due to the ICL labeling or complement attack and was observed after
266 of the non-ubiquitinated ID complex bound to ICL DNA-which we also report here-we show that monoubiqu
267 -associated nuclease 1 (FAN1) contributes to ICL repair, FAN1 mutations predispose to karyomegalic in
271 arrying BRCA2 DBD mutations are sensitive to ICL-inducing agents but resistant to HU treatment consis
278 ordinates multiple endonucleases that unhook ICLs, resolve homologous recombination intermediates, an
279 for the incisions that release, or "unhook", ICLs, but the mechanism of ICL unhooking remains largely
282 imics the complete processing of an unhooked ICL to a single crosslinked nucleotide, and find that it
286 of incisions and processing of the unhooked ICLs significantly influence the efficiency and fidelity
288 from Fan1(nd/nd) mice become polyploid upon ICL induction, suggesting that defective ICL repair caus
291 achieved by sulcus implantation of a Visian ICL (STAAR Surgical, Monrovia, California, USA) under ge
300 depletion sensitized cells to treatment with ICL-inducing agents and led to accumulation of cells in