Effect of G: C→A:T transition, potentially arising from O6-guanine alkylation, in the transcription regulation of c-fos serum response element

Marina Bonfanti, Gennaro Colella, Massimo Broggini, Maurizio D'Incalci

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Abstract

O6-meGs, if not repaired before cell undergo DNA synthesis, can cause erroneous pairing of thymine resulting in a G:C→A:T transition, after the next DNA replication. It is known that the presence of O6-meG in promoter sequences inhibits the specific binding of transcription factors. Little is known on the effect of G:C→A:T transitions on this binding. c-fos SRE was used as a model to study the effect of different G:C→A:T transitions (at the positions -305, -306, -316, -319 and -320) in terms of SRE specific DNA-binding and functional ability to activate transcription of a reporter gene. The electromobility shift assay and a transient transfection assay were used. The G:C→A:T transition at -320 caused 92% inhibition, while mutations at the positions -305, -306, -316 and-319 caused respectively 55, 43, 19 and 44% inhibition. The findings indicate that some G:C→A:T transitions, potentially arising from O6-guanine methylation, can impair the regulation of c-fos transcription.

Original languageEnglish
Pages (from-to)2019-2024
Number of pages6
JournalAnticancer Research
Volume17
Issue number3 C
Publication statusPublished - 1997

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Keywords

  • Alkylating agents
  • Gene
  • Point mutations
  • Transcription

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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