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

PeerJ

article

Caroline Zutterling¹  Aibek Mursalimov²  Ibtissam Talhaoui³  Zhanat Koshenov²  Zhiger Akishev⁴  Amangeldy K. Bissenbaev⁴  Gerard Mazon³  Nicolas E. Geacintov⁵  Didier Gasparutto⁶  Regina Groisman¹  Dmitry O. Zharkov⁷  Bakhyt T. Matkarimov²  Murat Saparbaev¹ 

[1] Groupe «Réparation de l’ADN», Equipe Labellisée par la Ligue Nationale Contre le Cancer, CNRS UMR8200, Université Paris-Sud, Gustave Roussy Cancer Campus;National Laboratory Astana, Nazarbayev University;CNRS UMR 8200—Laboratoire «Stabilité Génétique et Oncogenèse», Université Paris Sud ,(Paris XI), Gustave Roussy Cancer Campus;Department of Molecular Biology and Genetics, al-Farabi Kazakh National University, Faculty of Biology;Chemistry Department, New York University;CEA, CNRS, INAC, SyMMES, Université Grenoble Alpes;SB RAS Institute of Chemical Biology and Fundamental Medicine;Novosibirsk State University

关键词: Adenine-DNA glycosylase;    Nucleotide excision repair;    UV-induced mutagenesis;    Cyclobutane pyrimidine dimer;    Base excision repair;    Aberrant DNA repair;    Escherichia coli;    Pyrimidine (6–4) pyrimidone photoproduct;   

DOI  :  10.7717/peerj.6029

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY