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dc.contributor.authorTesfahun, Almaz Nigatu
dc.contributor.authorAlexeeva, Marina
dc.contributor.authorTomkuvienė, Miglė
dc.contributor.authorArshad, Aysha
dc.contributor.authorGuragain, Prashanna
dc.contributor.authorKlungland, Arne
dc.contributor.authorKlimašauskas, Saulius
dc.contributor.authorRuoff, Peter
dc.contributor.authorBjelland, Svein
dc.identifier.citationTesfahun, A.N., Alexeeva, M., Tomkuviene, M. et al. (2021) Alleviation of C⋅C Mismatches in DNA by the Escherichia coli Fpg Protein. Frontiers in Microbiology,en_US
dc.description.abstractDNA polymerase III mis-insertion may, where not corrected by its 3′→ 5′ exonuclease or the mismatch repair (MMR) function, result in all possible non-cognate base pairs in DNA generating base substitutions. The most thermodynamically unstable base pair, the cytosine (C)⋅C mismatch, destabilizes adjacent base pairs, is resistant to correction by MMR in Escherichia coli, and its repair mechanism remains elusive. We present here in vitro evidence that C⋅C mismatch can be processed by base excision repair initiated by the E. coli formamidopyrimidine-DNA glycosylase (Fpg) protein. The kcat for C⋅C is, however, 2.5 to 10 times lower than for its primary substrate 8-oxoguanine (oxo8G)⋅C, but approaches those for 5,6-dihydrothymine (dHT)⋅C and thymine glycol (Tg)⋅C. The KM values are all in the same range, which indicates efficient recognition of C⋅C mismatches in DNA. Fpg activity was also exhibited for the thymine (T)⋅T mismatch and for N4- and/or 5-methylated C opposite C or T, Fpg activity being enabled on a broad spectrum of DNA lesions and mismatches by the flexibility of the active site loop. We hypothesize that Fpg plays a role in resolving C⋅C in particular, but also other pyrimidine⋅pyrimidine mismatches, which increases survival at the cost of some mutagenesis.en_US
dc.publisherFrontiers Media S.Aen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.subjectEscherichia colien_US
dc.titleAlleviation of C⋅C Mismatches in DNA by the Escherichia coli Fpg Proteinen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.rights.holderCopyright © 2021 Tesfahun, Alexeeva, Tomkuviene, Arshad, Guragain, Klungland, ˙ Klimašauskas, Ruoff and Bjelland.en_US
dc.subject.nsiVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Generell mikrobiologi: 472en_US
dc.source.journalFrontiers in Microbiologyen_US

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal