Highly Mutagenic Exocyclic DNA Adducts Are Substrates for the Human Nucleotide Incision Repair Pathway

Paulina Prorok (1) , Christine Saint-Pierre (2, 3) , Didier Gasparutto (3, 2) , Olga Fedorova (4) , Alexander Ishchenko (1) , Hervé Leh (5) , Malcolm Buckle (5) , Barbara Tudek (1) , Murat Saparbaev (1)

1 CNRS UMR 8200 - Réparation de l’ADN
2 LAN - Laboratoire Lésions des Acides Nucléiques
3 SCIB - UMR E3 - Service de Chimie Inorganique et Biologique
4 ICBFM SB RAS - Institute of Chemical Biology and Fundamental Medicine [Novosibirsk, Russia]
5 LBPA - Laboratoire de Biologie et de Pharmacologie Appliquée

Background: Oxygen free radicals induce lipid peroxidation (LPO) that damages and breaks polyunsaturated fatty acids in cell membranes. LPO-derived aldehydes and hydroxyalkenals react with DNA leading to the formation of etheno(e)-bases including 1,N 6-ethenoadenine (eA) and 3,N 4-ethenocytosine (eC). The eA and eC residues are highly mutagenic in mammalian cells and eliminated in the base excision repair (BER) pathway and/or by AlkB family proteins in the direct damage reversal process. BER initiated by DNA glycosylases is thought to be the major pathway for the removal of non-bulky endogenous base damage. Alternatively, in the nucleotide incision repair (NIR) pathway, the apurinic/apyrimidinic (AP) endonucleases can directly incise DNA duplex 59 to a damaged base in a DNA glycosylase-independent manner.

Domaines: Sciences du Vivant [q-bio]; Biochimie, Biologie Moléculaire

Paulina Prorok, Christine Saint-Pierre, Didier Gasparutto, Olga Fedorova, Alexander Ishchenko, et al.. Highly Mutagenic Exocyclic DNA Adducts Are Substrates for the Human Nucleotide Incision Repair Pathway. PLoS ONE, 2012, 7 (12), pp.e51776. ⟨10.1371/journal.pone.0051776⟩. ⟨hal-02368498⟩