Thymidylate synthase inhibition in cells with arrested DNA synthesis is not due to an allosteric interaction in the replitase complex

Wojciech Rode, Malgorzata M. Jastreboff, Joseph R. Bertino

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Activity of thymidylate synthase was measured in situ in leukemia cells by tritium release from [5-3H]dUrd. Aphidicolin, an inhibitor of DNA polymerase α, but not thymidylate synthase, caused a time dependent inhibition of the enzyme when added to the cells after [5-3H]dUrd. Cells treated with hydroxyurea and aphidicolin in sequence before addition of [5-3H]dUrd had a high initial thymidylate synthase activity that decreased with time. This pattern indicates that thymidylate synthase activity is linked to DNA synthesis; however, its inhibition by drugs that inhibit DNA synthesis may be due to accumulation of thymidine nucleotide(s), rather than to an allosteric interaction in the replitase complex.

Original languageEnglish (US)
Pages (from-to)345-351
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume128
Issue number1
DOIs
StatePublished - Apr 16 1985
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biophysics
  • Biochemistry
  • Cell Biology

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