Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli

Caroline Zutterling (1) , Aibek Mursalimov (2) , Ibtissam Talhaoui (3) , Zhanat Koshenov (2) , Zhiger Akishev (4) , Amangeldy Bissenbaev (5) , Gerard Mazon (3) , Nicolas E Geacintov , Didier Gasparutto (6, 7) , Regina Groisman (8) , Dmitry Zharkov (9) , Bakhyt Matkarimov (2) , Murat Saparbaev (3)

1 CNRS UMR 8200 - Réparation de l’ADN
2 National Laboratory Astana
3 UMR 8200 - Stabilité Génétique et Oncogenèse
4 Department of Molecular Biology and Genetics
5 KazNU - Al-Farabi Kazakh National University [Almaty]
6 CREAB - Chimie pour la Reconnaissance et l’Etude d’Assemblages Biologiques
7 SYMMES - SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé
8 Laboratoire Epigenetique et Cancer
9 NSU - Novosibirsk State University

Background: DNA repair is essential to counteract damage to DNA induced by endo-and exogenous factors, to maintain genome stability. However, challenges to the faithful discrimination between damaged and non-damaged DNA strands do exist, such as mismatched pairs between two regular bases resulting from spontaneous deamination of 5-methylcytosine or DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved the mismatch-specific DNA glycosylases that can recognize and remove regular DNA bases in the mismatched DNA duplexes. The Escherichia coli adenine-DNA glycosylase (MutY/MicA) protects cells against oxidative stress-induced mutagenesis by removing adenine which is mispaired with 7,8-dihydro-8-oxoguanine (8oxoG) in the base excision repair pathway. However, MutY does not discriminate between template and newly synthesized DNA strands. Therefore the ability to remove A from 8oxoG•A mispair, which is generated via misincorporation of an 8-oxo-2′-deoxyguanosine-5′-triphosphate precursor during DNA replication and in which A is the template base, can induce A•T/C•G transversions. Furthermore, it has been demonstrated that human MUTYH, homologous to the bacterial MutY, might be involved in the aberrant processing of ultraviolet (UV) induced DNA damage. Methods: Here, we investigated the role of MutY in UV-induced mutagenesis in E. coli. MutY was probed on DNA duplexes containing cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproduct (6-4PP). UV irradiation of E. coli induces Save Our Souls (SOS) response characterized by increased production of DNA repair enzymes and mutagenesis. To study the role of MutY in vivo, the mutation frequencies to rifampicin-resistant (RifR) after UV irradiation of wild type and mutant E. coli strains were measured. Results: We demonstrated that MutY does not excise Adenine when it is paired with CPD and 6–4PP adducts in duplex DNA. At the same time, MutY excises Adenine in A•G and A•8oxoG mispairs. Interestingly, E. coli mutY strains, which have elevated spontaneous mutation rate, exhibited low mutational induction after UV exposure as compared to MutY-proficient strains. However, sequence analysis of RifR mutants revealed that the frequencies of C/T transitions dramatically increased after UV irradiation in both MutY-proficient and -deficient E. coli strains. Discussion: These findings indicate that the bacterial MutY is not involved in the aberrant DNA repair of UV-induced DNA damage

Domaines: Sciences du Vivant [q-bio]; Biochimie, Biologie Moléculaire; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Caroline Zutterling, Aibek Mursalimov, Ibtissam Talhaoui, Zhanat Koshenov, Zhiger Akishev, et al.. Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli. PeerJ, 2018, 6, pp.e6029. ⟨10.7717/peerj.6029⟩. ⟨hal-02322261⟩