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1 d exclusively on ThyX activity to synthesize thymidylate.
2 ynthesis of the sole de novo source of deoxy-thymidylate.
3 lyzes the intracellular de novo formation of thymidylate (a DNA building block) in most living organi
4 sequence, and the rate of excision of these thymidylate analogues was greater than or equal to that
5 re required for the synthesis of purines and thymidylate and for S-adenosylmethionine (AdoMet)-depend
8 nation of the specific contributions made by thymidylate and S-adenosylmethionine biosynthesis to CRC
10 arbons for the de novo synthesis of purines, thymidylate, and for the remethylation of homocysteine t
12 quired for the de novo synthesis of purines, thymidylate, and S-adenosylmethionine, the primary cellu
13 sulting in enhanced folate-dependent de novo thymidylate biosynthesis and impaired homocysteine remet
15 of Shmt1 expression causes NTDs by impairing thymidylate biosynthesis and shows that changes in the e
16 artitions folate-derived one-carbon units to thymidylate biosynthesis at the expense of cellular meth
17 te is preferentially directed toward de novo thymidylate biosynthesis at the expense of homocysteine
19 cate a mechanism that is very different from thymidylate biosynthesis in humans, underscoring the pro
20 methylenetetrahydrofolate cofactors and that thymidylate biosynthesis is preserved in folate deficien
21 midylate synthesis and indicate that de novo thymidylate biosynthesis occurs at replication forks.
22 ependent nuclear localization of the de novo thymidylate biosynthesis pathway and a decrease in DNA s
23 artmentation of the folate-dependent de novo thymidylate biosynthesis pathway in the nucleus accounts
24 ependent enzymes that constitute the de novo thymidylate biosynthesis pathway, cSHMT, thymidylate syn
26 hether a corresponding disruption in de novo thymidylate biosynthesis underlies NTD pathogenesis.
28 s 5,10-methylenetetrahydrofolate for de novo thymidylate biosynthesis, a limiting step in the pathway
29 result of impaired folate-dependent de novo thymidylate biosynthesis, a pathway composed of the enzy
30 MT1 and TYMS, lower rates of nuclear de novo thymidylate biosynthesis, and a nearly 10-fold increase
35 rived folate-activated one-carbon units into thymidylate biosynthesis; the efficiency of nuclear fola
37 (SUMO)- and folate-dependent nuclear de novo thymidylate (dTMP) biosynthesis is a sensitive target of
40 efects (NTDs) indicate that impaired de novo thymidylate (dTMP) synthesis through changes in SHMT exp
41 ), which provides the sole de novo source of thymidylate (i.e., the DNA base T) for most organisms.
42 the final step in this de novo production of thymidylate in many human pathogens, but it is absent fr
48 112 gene was predicted to encode a fusion of thymidylate kinase (tmk) and dUTP diphosphatase (dut).
54 on DHFR protein levels was specific, because thymidylate kinase and thymidylate synthase protein leve
56 ch as flavin-dependent thymidylate synthase, thymidylate kinase, ribonucleotide reductase, and deoxyc
57 y potency against Mycobacterium tuberculosis thymidylate kinase, the target of the 3-cyanopyridones t
59 l lid similar to the structures of microbial thymidylate kinases, suggesting that these proteins shar
68 al targets including dihydrofolate reductase-thymidylate synthase (DHFR-TS) and inosine monophosphate
70 ckout (DKO) lines of dihydrofolate reductase-thymidylate synthase (DHFR-TS) of bloodstream Trypanosom
72 strate is the pyrimidine biosynthetic enzyme thymidylate synthase (EC 2.1.1.45), which catalyzes the
74 man pathogens, thyX-encoded flavin-dependent thymidylate synthase (FDTS) catalyzes the last step in t
75 hyX gene, which codes for a flavin-dependent thymidylate synthase (FDTS), and is present in several h
76 gens rely on an alternative flavin-dependent thymidylate synthase (FDTS), which differs from the huma
79 ntiangiogenic effects and also inhibit human thymidylate synthase (hTS) for cytotoxic effects in sing
85 lasmodium falciparum dihydrofolate reductase-thymidylate synthase (P. falciparum DHFR-TS) with the ob
86 cobacterium bovis BCG with insertions in the thymidylate synthase (thyA) gene, a critical determinant
87 eles enhanced the survival of L. pneumophila thymidylate synthase (thyA)-deficient strains, which can
88 se (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untransl
89 uced folate carrier (RFC) 80A allele and the thymidylate synthase (TS) 3'-untranslated region (3'-UTR
90 ymidine to overcome the potent inhibition of thymidylate synthase (TS) and deoxycytidine monophosphat
91 ues 2a-2m were synthesized as potential dual thymidylate synthase (TS) and dihydrofolate reductase (D
92 gues 5-13 were synthesized as potential dual thymidylate synthase (TS) and dihydrofolate reductase (D
93 nclassical analogues 5- 15 as potential dual thymidylate synthase (TS) and dihydrofolate reductase (D
94 onclassical analogues 5-17 as potential dual thymidylate synthase (TS) and dihydrofolate reductase (D
95 and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (D
96 rotozoal parasites are unusual in that their thymidylate synthase (TS) and dihydrofolate reductase (D
104 rements for I-TevI, which binds a stretch of thymidylate synthase (TS) DNA that codes for functionall
106 s have investigated the relationship between thymidylate synthase (TS) expression and survival in col
107 e thyX gene and depend upon the conventional thymidylate synthase (TS) for their dTMP requirements.
108 nd possibly more effective way of inhibiting thymidylate synthase (TS) in cells than through the use
109 PYD expression by p53 is augmented following thymidylate synthase (TS) inhibition and DPYD repression
110 now known as ONX 0801), is a small molecule thymidylate synthase (TS) inhibitor discovered at the In
111 sing levels of dUTPase on sensitivity to the thymidylate synthase (TS) inhibitor fluorodeoxyuridine (
112 and toxicity of clinically used folate-based thymidylate synthase (TS) inhibitors that require folylp
119 ur laboratory have shown that translation of thymidylate synthase (TS) mRNA is controlled by its own
121 antimetabolite radiosensitizers may inhibit thymidylate synthase (TS) or ribonucleotide reductase, a
122 esidues on the RNA binding activity of human thymidylate synthase (TS) was investigated by mutating e
124 tifolates on dihydrofolate reductase (DHFR), thymidylate synthase (TS), and folylpolyglutamate synthe
125 onucleases that bind a homologous stretch of thymidylate synthase (TS)-encoding DNA but use different
126 degraded siRNAs reversed the cytotoxicity of thymidylate synthase (TS)-targeted siRNAs and other TS i
130 athway is the pyrimidine biosynthetic enzyme thymidylate synthase (TS; EC 2.1.1.45), which catalyzes
135 es are involved in the reaction catalyzed by thymidylate synthase (TSase), which provides the sole de
139 enetetrahydrofolate reductase (MTHFR) 677TT, thymidylate synthase (TSER) *2/*2 (variable number of ta
140 s examined and haplotypes generated included thymidylate synthase (TYMS 28-bp triple repeat [3R]-->do
141 , where they form a multienzyme complex with thymidylate synthase (TYMS) and dihydrofolate reductase
142 hylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) are known to play a role in
143 uiescence through the cell cycle, regulating thymidylate synthase (Tyms) expression at the G(1)/S bou
144 ng required for activating expression of the thymidylate synthase (Tyms) gene at the G1/S transition.
145 erest because it contained the gene encoding thymidylate synthase (TYMS), a molecular target of 5-FU.
146 ial serine hydroxymethyltransferase (SHMT2), thymidylate synthase (TYMS), and a novel human mitochond
147 ymes serine hydroxymethyltransferase (SHMT), thymidylate synthase (TYMS), and dihydrofolate reductase
148 he transcriptional status of four key genes, thymidylate synthase (TYMS), MORF-related gene X (MRGX),
150 d to elevated expression of the main target, thymidylate synthase (TYMS), which catalyses the de novo
152 seem, based on accumulated literature, to be thymidylate synthase (TYMS, TS) expression levels, TS ge
156 of both endogenous and ectopically expressed thymidylate synthase alleles revealed that the mRNA-bind
157 negatively charged dihydrofolate produced at thymidylate synthase and a series of lysine and arginine
159 enzymes in its biosynthetic pathway, namely thymidylate synthase and cytoplasmic thymidine kinase.
160 by the fact that a 100-fold up-regulation of thymidylate synthase and dihydrofolate reductase (known
161 and trimethoprim (TOP), potent inhibitors of thymidylate synthase and dihydrofolate reductase, respec
163 thought to kill cells via the inhibition of thymidylate synthase and increased use of dUTP in place
165 apeutics, including dihydrofolate reductase, thymidylate synthase and ribonucleotide reductase, while
167 and cellular morphology between H630 and the thymidylate synthase and rTSbeta-overproducing, 5-FU-res
168 tide reductase, dihydrofolate reductase, and thymidylate synthase are coordinately regulated to ensur
171 tification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced
174 ium tuberculosis and dihydrofolate reductase/thymidylate synthase from Babesia bovis, against 48 diff
176 crystal structure of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis and a
179 present study, we identified an orthologous thymidylate synthase gene in the relapsing fever (RF) ag
180 homing endonuclease I-TevI that targets the thymidylate synthase gene of phage T4, we readily isolat
181 orphism in the 3'-untranslated region of the thymidylate synthase gene was shown to influence mRNA st
182 ich targets a different cleavage site in the thymidylate synthase gene, recapitulating the evolution
183 interleukin-6, dihydrofolate reductase, and thymidylate synthase genes were identified, along with a
184 ta suggest that BGC 945 selectively inhibits thymidylate synthase in alpha-FR-overexpressing tumors a
186 nd FdU misincorporation sites resulting from thymidylate synthase inhibition and thymine depletion.
187 ng gemcitabine uptake or gemcitabine-induced thymidylate synthase inhibition, and only reflected grow
190 NG depletion does not sensitize cells to the thymidylate synthase inhibitor (raltitrexed), which indu
193 FdUMP[10] as well as to FdUMP, FdU, and the thymidylate synthase inhibitor raltitrexed (Tomudex).
194 BGC 945 is a cyclopenta[g]quinazoline-based, thymidylate synthase inhibitor specifically transported
195 nses (i.e. G(2) arrest and lethality) to the thymidylate synthase inhibitor, Tomudex, and a greater l
196 rouracil combined with leucovorin and to the thymidylate synthase inhibitor, ZD9331, dependent on thy
197 key determinant of tumor cell sensitivity to thymidylate synthase inhibitors such as 5-fluoro-2'-deox
198 positively regulates the cytotoxic action of thymidylate synthase inhibitors, negatively regulates th
200 '-deoxyuridine 5'-monophosphate (FdUMP), the thymidylate synthase inhibitory metabolite of 5-fluorour
203 e labeled cofactor in mechanistic studies of thymidylate synthase is demonstrated by measuring the tr
204 owed that intracellular proteolysis of human thymidylate synthase is directed by a degron at the poly
206 site CC genotype (OR, 4.5; P =.045), and the thymidylate synthase low activity 2/2 enhancer repeat ge
208 tide reductase, dihydrofolate reductase, and thymidylate synthase promoters in the absence of SWI/SNF
210 actone (3-oxo-C12-(L)-HSL) can down-regulate thymidylate synthase protein at 10 micromol/L and reduce
211 was specific, because thymidylate kinase and thymidylate synthase protein levels were not decreased n
213 ase is required to significantly inhibit the thymidylate synthase reaction, consistent with experimen
214 ar hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that
215 ourses (R(2) = 0.043; P < .001), whereas the thymidylate synthase rs34743033 tandem repeat polymorphi
217 ybaK for its ability to suppress the E. coli thymidylate synthase thyA:146CCA missense mutant strain,
220 se thymine depends on activity of the enzyme thymidylate synthase to catalyse the methylation of the
221 zation of dihydrofolate reductase, SHMT, and thymidylate synthase to the nuclear lamina, indicating t
223 trexed that combines enzymatic inhibition of thymidylate synthase with alpha-folate receptor-mediated
225 of a plant DHFR-TS (dihydrofolate reductase-thymidylate synthase) gene family that implements the pe
227 sites located immediately upstream of ORF70 (thymidylate synthase), ORF19 (tegument protein), and ORF
228 nophages, but also by all 27 T4-like phages (thymidylate synthase); its evolutionary history suggests
229 . coli NDP kinase interacts directly with T4 thymidylate synthase, aerobic ribonucleotide reductase,
230 and is a major supplier of the substrate for thymidylate synthase, an important enzyme in DNA synthes
231 ovo thymidylate biosynthesis pathway, cSHMT, thymidylate synthase, and dihydrofolate reductase, all c
233 e equivalent inhibition of the target enzyme thymidylate synthase, and instead accumulate progressive
234 sical thymidylate synthases, including human thymidylate synthase, and is instrumental in mechanism-b
236 sporter 1 (hENT1), thymidine kinase 1 (TK1), thymidylate synthase, and thymidine phosphorylase (TP) w
237 pend on the presence of intact gp32, notably thymidylate synthase, dihydrofolate (DHF) reductase, rib
238 regulators of antigen presentation, EZH2 and thymidylate synthase, enhanced DLBCL MHC-I presentation.
240 Expression of a series of six markers (p53, thymidylate synthase, glutathione s-transferase pi [GST-
241 therapeutic drug pemetrexed, an inhibitor of thymidylate synthase, has an important secondary target
242 titute for the IDR and the hA helix of human thymidylate synthase, indicating that the degradation-pr
243 amples for the detection of polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductas
246 nucleotide salvage, such as flavin-dependent thymidylate synthase, thymidylate kinase, ribonucleotide
249 s, rely on the thyA- or TYMS-encoded classic thymidylate synthase, whereas, certain microorganisms, i
250 ide thymidylate is synthesized by the enzyme thymidylate synthase, which catalyzes the reductive meth
252 One mutant, K282E/R283E, was found to be thymidylate synthase-dead because of an impaired ability
253 es examined, as did thymidine deprivation in thymidylate synthase-deficient (thymidylate synthase-) c
254 luated both in vivo, by complementation of a thymidylate synthase-deficient Escherichia coli mutant,
256 hat substrate channeling in the bifunctional thymidylate synthase-dihydrofolate reductase enzyme from
258 ions of rTS signaling mimics as enhancers to thymidylate synthase-directed chemotherapy, evidence tha
268 on of the recently crystallized bifunctional thymidylate synthasedihydrofolate reductase (TS-DHFR) en
269 rent chemical cascade than that of classical thymidylate synthases or any other known biological meth
271 ionality has been demonstrated for classical thymidylate synthases, including human thymidylate synth
272 of folate or vitamin B12 inhibits purine and thymidylate syntheses, impairs DNA synthesis, and causes
274 synthesis, affirming the competition between thymidylate synthesis and homocysteine remethylation for
275 Previous studies have indicated that the thymidylate synthesis and homocysteine remethylation pat
276 SHMT expression is rate-limiting for de novo thymidylate synthesis and indicate that de novo thymidyl
277 would support increased rates of purine and thymidylate synthesis and the provision of methionine fo
278 arbon metabolism, responsible for purine and thymidylate synthesis and transmethylation reactions, pl
280 was associated with a decreased capacity for thymidylate synthesis due to downregulation of enzymes i
285 indicate that SHMT1-mediated nuclear de novo thymidylate synthesis is critical for maintaining DNA in
286 nteraction, indicating that the capacity for thymidylate synthesis modifies susceptibility to intesti
288 etion of cytoplasmic FTHFS activity enhances thymidylate synthesis, affirming the competition between
289 in nuclear DNA, indicating enhanced de novo thymidylate synthesis, and suggesting that serine hydrox
290 ese are primarily used for purine synthesis, thymidylate synthesis, and the provision of methyl group
294 ductase 1 (PTR1) and dihydrofolate reductase-thymidylate synthetase (DHFR-TS) is commonly measured as
295 okinetics were obtained on all patients, and thymidylate synthetase (TS) activity was measured in per
296 ing mode for interactions of DNA primase and thymidylate synthetase (TS) with high and low affinity s
297 P = .03), which was further increased by the thymidylate synthetase (TYMS) 3/3 genotype (P = .03).
298 ere performed to evaluate the expressions of Thymidylate synthetase (TYMS), TP53 (p53), beta-catenin
299 s DNA synthesis by inhibiting the ability of thymidylate synthetase to produce dTMP, the drug also ha
300 zyme responsible for de novo biosynthesis of thymidylate (TMP) and is essential for cell proliferatio
301 a key metabolic function is the synthesis of thymidylate, which requires 5,10-methylenetetrahydrofola