3-Methyl-3-deazaadenine, a stable isostere of N3-methyl-adenine, is efficiently bypassed by replication in vivo and by transcription in vitro

Publication year: 2011
Source: DNA Repair, In Press, Corrected Proof, Available online 14 June 2011

Paola, Monti , Christopher, Broxson , Alberto, Inga , Ruo-wen, Wang , Paola, Menichini , …

The goal of the present work was to determine the impact of N3-methyladenine (3-mA), an important lesion generated by many environmental agents and anticancer drugs, on in vivo DNA replication and in vitro RNA transcription. Due to 3-mA chemical instability, the stable isostere 3-methyl-3-deazaadenine (3-m-c3A) was site specifically positioned into an oligodeoxynucleotide. The oligomer was, then incorporated into a vector system that is rapidly converted to ssDNA inside yeast cells and requires DNA replication opposite the lesion for plasmid clonal selection. For control purposes, an adenine or a stable apurinic/apyrimidinic (AP)-lesion was placed at the same site. The presence of…

 Highlights: ► The effects on DNA metabolism of a stable isostere of 3methyladenine, 3-methyl-3-deazaadenine (3-m-c3A), are presented. ► 3-m-c3A was site specifically positioned, and incorporated into a vector system that is converted to ssDNA inside yeast cells. ► 3-m-c3A does not significantly affect neither DNA replication in vivo nor RNA transcription in vitro. ► Considering bypass events opposite 3-m-c3A the absence of Polη was associated with an increase in AT>GC transitions.