Frank Maley

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PURPOSE To determine whether immunohistochemical thymidylate synthase (TS) quantitation predicts for clinical outcome in patients with advanced colorectal cancer treated by fluorouracil (FUra)-based chemotherapy. PATIENTS AND METHODS TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 48 patients(More)
Thymidylate synthase (TS) catalyzes the substitution of a carbon-bound proton in a uracil base by a methyl group to yield thymine in the de novo biosynthesis of this DNA base. The enzymatic mechanism involves making and breaking several covalent bonds. Traditionally, a conserved tyrosine (Y94 in Escherichia coli, Y146 in Lactobacillus casei, and Y135 in(More)
The nature of a H-transfer in the thymidylate synthase catalyzed reaction was investigated by comparison of the wild-type enzyme with the W80M mutant. The nature of the H-transfer was not affected, as indicated by intrinsic isotope effects and their temperature dependence. These findings support a single-step hydride transfer instead of a two-step radical(More)
The td gene contains a 735 bp open reading frame within its 1017 bp intron. A 12 nucleotide stretch may form a stable secondary structure with the putative Shine-Dalgarno sequence of the intron open reading frame and thus impair its translation. SP6 RNA polymerase transcripts of the td gene synthesized in vitro at 40 degrees C encompass a 2.7 kb primary(More)
The chlorovirus PBCV-1, like many large double-stranded DNA-containing viruses, contains several genes that encode putative proteins involved in nucleotide biosynthesis. This report describes the characterization of the PBCV-1 dCMP deaminase, which produces dUMP, a key intermediate in the synthesis of dTTP. As predicted, the recombinant protein has dCMP(More)
  • L L M Van Deenen, Utrecht, P Borst, Amsterdam, G K Radda, P Cohen +119 others
  • 2012
Studies on monomolecular layers of phospholipids containing the antenna protein B800-850 (LHCP) and in some cases additionally the reaction center of the photosynthetic bacterium Rhodopseudomonas sphaeroides are reported. Information on monolayer preparation as well as on protein /lipid and protein/protein interaction is obtained by means of fluorescence(More)
Numerous reports describe the phage T4 enzymes thymidylate synthase and dihydrofolate reductase as structural components of the baseplate. However, Y. Wang and C. K. Mathews (J. Virol. 63:4736-4743, 1989) reported that antisera against the respective recombinant enzymes failed to neutralize phage infectivity, in contrast to previous results. Moreover, a(More)
The interrupted T4 phage td gene, which encodes thymidylate synthase, is the first known example of an intron-containing prokaryotic structural gene. Analysis of td-encoded transcripts provides evidence in favor of maturation at the RNA level. Northern blotting with T4 RNA and with region-specific probes revealed three classes of RNA: diffuse premessage(More)
Potential changes in liver protein biosynthesis were investigated in 1 to 10-month-old male Fischer F344 rats by isolation and translation of polysome-derived poly(A)-containing RNA and by incubation of isolated hepatocytes in Swim's S77 medium supplemented with [3H]leucine. Labeled protein products were analyzed by one- and two-dimensional polyacrylamide(More)
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