Alternative DNA repair pathways to handle complex DNA damage generated by oxidative stress and anticancer drugs

E. Matta (1) , U. Aliyaskarova (1) , A. A Kuznetsova (2) , B. T Matkarimov (3) , O. S Fedorova (2) , N. A Kuznetsov (2) , Alexander Ishchenko (1) , M. Saparbaev (1)

1 CNRS UMR 8200 - Réparation de l’ADN
2 ICBFM SB RAS - Institute of Chemical Biology and Fundamental Medicine [Novosibirsk, Russia]
3 Nazarbayev University [Kazakhstan]

The clinical features of inherited human DNA repair-deficient disorders such as Cockayne syndrome and Fanconi anemia point to the complex nature of endogenous oxidative DNA damage, which may include bulky adducts, inter-strand DNA crosslinks (ICLs) and clustered lesions. Conversely, severe biological effects of DNA crosslinking agents and ionizing radiation correlated with formation of ICLs and double-strand breaks in DNA, respectively. These complex DNA damages are postulated to be critical because they are more difficult to repair than singular lesions. It anticipated that the removal of ICLs and clustered oxidatively-induced DNA bases on both strands would, if not tightly regulated, either inhibit certain steps of repair or produce persistent chromosome breaks and thus be lethal for the cells. Genetic and biochemical data indicate that the elimination of complex damages requires several distinct DNA repair pathways including: base excision repair, nucleotide incision repair, Poly(ADP-ribose) polymerases-mediated DNA strand break repair, global genome and transcription-coupled nucleotide excision repair, mismatch repair, homologous recombination, non-homologous end joining, and translesion DNA synthesis pathways. In this review, we describe the role of recently discovered alternative DNA repair pathways in the removal of complex DNA lesions.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]

E. Matta, U. Aliyaskarova, A. A Kuznetsova, B. T Matkarimov, O. S Fedorova, et al.. Alternative DNA repair pathways to handle complex DNA damage generated by oxidative stress and anticancer drugs. Miral Dizdaroglu; R Stephen Lloyd. DNA Damage, DNA Repair and Disease, 1, Royal Society of Chemistry, pp.249-278, 2020, 978-1-78801-889-0. ⟨10.1039/9781839160769-00249⟩. ⟨hal-03301429⟩