Incorporation of a minimal nucleotide into DNA

Pascal Röthlisberger (1) , Fabienne Levi-Acobas (1) , Ivo Sarac (1) , Rémy Ricoux (2) , Jean-Pierre Mahy (2) , Piet Herdewijn (3) , Philippe Marlière (4) , Marcel Hollenstein (1)

1 Chimie bioorganique des acides nucléiques - Bioorganic chemistry of nucleic acids
2 ICMMO - Institut de Chimie Moléculaire et des Matériaux d'Orsay
3 Rega Institute for Medical Research [Leuven, België]
4 ISSB - Institut de biologie systémique et synthétique

Abasic sites are amongst the most frequent DNA lesions and result from spontaneous hydrolysis of the glycosidic bond or from the removal of damaged nucleobases. These depurination events can also occur on free deoxyribonucleoside triphosphates present in cells and lead to the formation of an abasic site triphosphate of which very little is known. Herein, we report the synthesis and biochemical characterization of the minimal triphosphate dФTP. Unexpectedly, dФTP is tolerated by various DNA polymerases and the incorporation efficiency obeys the A-rule. Single incorporation of dФMP units were also observed opposite abasic sites and the addition of prosthetic molecules mimicking base-pairs do not seem to favor the process.

Keywords: Copper complex; Perylene bisimide; Primer extension reactions; Abasic nucleoside analogues; Nucleoside triphosphate

Domains: Chemical Sciences; Chemical Sciences; Organic chemistry

Pascal Röthlisberger, Fabienne Levi-Acobas, Ivo Sarac, Rémy Ricoux, Jean-Pierre Mahy, et al.. Incorporation of a minimal nucleotide into DNA. Tetrahedron Letters, 2018, 59 (48), pp.4241-4244. ⟨10.1016/j.tetlet.2018.10.036⟩. ⟨pasteur-02012227⟩