Structural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNA

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dc.contributor.authorRedrejo-Rodríguez, Modesto
dc.contributor.authorVigouroux, Armelle
dc.contributor.authorMursalimov, Aibek
dc.contributor.authorGrin, Inga
dc.contributor.authorAlili, Doria
dc.contributor.authorKoshenov, Zhanat
dc.contributor.authorAkishev, Zhiger
dc.contributor.authorMaksimenko, Andrei
dc.contributor.authorBissenbaev, Amangeldy K.
dc.contributor.authorMatkarimov, Bakhyt T.
dc.contributor.authorSaparbaev, Murat
dc.contributor.authorIshchenko, Alexander A.
dc.contributor.authorMoréra, Solange
dc.creatorModesto, Redrejo-Rodríguez
dc.date.accessioned2018-01-04T10:43:43Z
dc.date.available2018-01-04T10:43:43Z
dc.date.issued2016-09-01
dc.description.abstractAbstract Oxidatively damaged DNA bases are substrates for two overlapping repair pathways: DNA glycosylase-initiated base excision repair (BER) and apurinic/apyrimidinic (AP) endonuclease-initiated nucleotide incision repair (NIR). In the BER pathway, an AP endonuclease cleaves DNA at AP sites and 3′-blocking moieties generated by DNA glycosylases, whereas in the NIR pathway, the same AP endonuclease incises DNA 5′ to an oxidized base. The majority of characterized AP endonucleases possess classic BER activities, and approximately a half of them can also have a NIR activity. At present, the molecular mechanism underlying DNA substrate specificity of AP endonucleases remains unclear mainly due to the absence of a published structure of the enzyme in complex with a damaged base. To identify critical residues involved in the NIR function, we performed biochemical and structural characterization of Bacillus subtilis AP endonuclease ExoA and compared its crystal structure with the structures of other AP endonucleases: Escherichia coli exonuclease III (Xth), human APE1, and archaeal Mth212. We found conserved amino acid residues in the NIR-specific enzymes APE1, Mth212, and ExoA. Four of these positions were studied by means of point mutations in APE1: we applied substitution with the corresponding residue found in NIR-deficient E. coli Xth (Y128H, N174Q, G231S, and T268D). The APE1-T268D mutant showed a drastically decreased NIR activity and an inverted Mg2+ dependence of the AP site cleavage activity, which is in line with the presence of an aspartic residue at the equivalent position among other known NIR-deficient AP endonucleases. Taken together, these data show that NIR is an evolutionarily conserved function in the Xth family of AP endonucleases.en_US
dc.identifierDOI:10.1016/j.biochi.2016.06.011
dc.identifier.citationModesto Redrejo-Rodríguez, Armelle Vigouroux, Aibek Mursalimov, Inga Grin, Doria Alili, Zhanat Koshenov, Zhiger Akishev, Andrei Maksimenko, Amangeldy K. Bissenbaev, Bakhyt T. Matkarimov, Murat Saparbaev, Alexander A. Ishchenko, Solange Moréra, Structural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNA, In Biochimie, Volumes 128–129, 2016, Pages 20-33en_US
dc.identifier.issn03009084
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0300908416301201
dc.identifier.urihttp://nur.nu.edu.kz/handle/123456789/3104
dc.language.isoenen_US
dc.publisherBiochimieen_US
dc.relation.ispartofBiochimie
dc.rights.license© 2016 The Authors. Published by Elsevier B.V.
dc.subjectOxidative DNA damageen_US
dc.subjectCrystal structureen_US
dc.subjectBase excision repairen_US
dc.subjectNucleotide incision repairen_US
dc.subjectAP endonucleaseen_US
dc.titleStructural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNAen_US
dc.typeArticleen_US
elsevier.aggregationtypeJournal
elsevier.coverdate2016-09-01
elsevier.coverdisplaydateSeptember–October 2016
elsevier.endingpage33
elsevier.identifier.doi10.1016/j.biochi.2016.06.011
elsevier.identifier.eid1-s2.0-S0300908416301201
elsevier.identifier.piiS0300-9084(16)30120-1
elsevier.identifier.pubmedid27343627
elsevier.identifier.scopusid84978153667
elsevier.openaccess1
elsevier.openaccessarticletrue
elsevier.openaccessuserlicensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
elsevier.openarchivearticlefalse
elsevier.startingpage20
elsevier.teaserOxidatively damaged DNA bases are substrates for two overlapping repair pathways: DNA glycosylase-initiated base excision repair (BER) and apurinic/apyrimidinic (AP) endonuclease-initiated nucleotide...
elsevier.volume128–129
workflow.import.sourcescience

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