TY - JOUR
T1 - Effect of G
T2 - C→A:T transition, potentially arising from O6-guanine alkylation, in the transcription regulation of c-fos serum response element
AU - Bonfanti, Marina
AU - Colella, Gennaro
AU - Broggini, Massimo
AU - D'Incalci, Maurizio
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Alkylating agents
KW - Gene
KW - Point mutations
KW - Transcription
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M3 - Article
C2 - 9216659
AN - SCOPUS:0030860480
VL - 17
SP - 2019
EP - 2024
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 3 C
ER -