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

Caroline Zutterling, Aibek Mursalimov, Ibtissam Talhaoui, Zhanat Koshenov, Zhiger Akishev, Amangeldy K. Bissenbaev, Gerard Mazon, Nicolas E. Geacintov, Didier Gasparutto, Regina Groisman, Dmitry O. Zharkov, Bakhyt Matkarimov, Murat Saparbaev

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere6029
JournalPeerJ
Volume2018
Issue number12
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

DNA Glycosylases
glycosylases
Mutagenesis
Adenine
adenine
mutagenesis
Escherichia coli
Repair
DNA
DNA Repair
DNA repair
DNA Damage
Pyrimidine Dimers
Genomic Instability
pyrimidines
Mutation Rate
Rifampin
rifampicin
irradiation
Pyrimidinones

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Zutterling, C., Mursalimov, A., Talhaoui, I., Koshenov, Z., Akishev, Z., Bissenbaev, A. K., ... Saparbaev, M. (2018). Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli. PeerJ, 2018(12), [e6029]. https://doi.org/10.7717/peerj.6029

Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli. / Zutterling, Caroline; Mursalimov, Aibek; Talhaoui, Ibtissam; Koshenov, Zhanat; Akishev, Zhiger; Bissenbaev, Amangeldy K.; Mazon, Gerard; Geacintov, Nicolas E.; Gasparutto, Didier; Groisman, Regina; Zharkov, Dmitry O.; Matkarimov, Bakhyt; Saparbaev, Murat.

In: PeerJ, Vol. 2018, No. 12, e6029, 01.01.2018.

Research output: Contribution to journalArticle

Zutterling, C, Mursalimov, A, Talhaoui, I, Koshenov, Z, Akishev, Z, Bissenbaev, AK, Mazon, G, Geacintov, NE, Gasparutto, D, Groisman, R, Zharkov, DO, Matkarimov, B & Saparbaev, M 2018, 'Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli' PeerJ, vol. 2018, no. 12, e6029. https://doi.org/10.7717/peerj.6029
Zutterling C, Mursalimov A, Talhaoui I, Koshenov Z, Akishev Z, Bissenbaev AK et al. Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli. PeerJ. 2018 Jan 1;2018(12). e6029. https://doi.org/10.7717/peerj.6029
Zutterling, Caroline ; Mursalimov, Aibek ; Talhaoui, Ibtissam ; Koshenov, Zhanat ; Akishev, Zhiger ; Bissenbaev, Amangeldy K. ; Mazon, Gerard ; Geacintov, Nicolas E. ; Gasparutto, Didier ; Groisman, Regina ; Zharkov, Dmitry O. ; Matkarimov, Bakhyt ; Saparbaev, Murat. / Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli. In: PeerJ. 2018 ; Vol. 2018, No. 12.
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T1 - Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli

AU - Zutterling, Caroline

AU - Mursalimov, Aibek

AU - Talhaoui, Ibtissam

AU - Koshenov, Zhanat

AU - Akishev, Zhiger

AU - Bissenbaev, Amangeldy K.

AU - Mazon, Gerard

AU - Geacintov, Nicolas E.

AU - Gasparutto, Didier

AU - Groisman, Regina

AU - Zharkov, Dmitry O.

AU - Matkarimov, Bakhyt

AU - Saparbaev, Murat

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N2 - 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.

AB - 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.

KW - Aberrant DNA repair

KW - Adenine-DNA glycosylase

KW - Base excision repair

KW - Cyclobutane pyrimidine dimer

KW - Escherichia coli

KW - Nucleotide excision repair

KW - Pyrimidine (6–4) pyrimidone photoproduct

KW - UV-induced mutagenesis

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