Alleviation of C⋅C Mismatches in DNA by the Escherichia coli Fpg Protein
dc.contributor.author | Tesfahun, Almaz Nigatu | |
dc.contributor.author | Alexeeva, Marina | |
dc.contributor.author | Tomkuvienė, Miglė | |
dc.contributor.author | Arshad, Aysha | |
dc.contributor.author | Guragain, Prashanna | |
dc.contributor.author | Klungland, Arne | |
dc.contributor.author | Klimašauskas, Saulius | |
dc.contributor.author | Ruoff, Peter | |
dc.contributor.author | Bjelland, Svein | |
dc.date.accessioned | 2021-09-28T13:16:58Z | |
dc.date.available | 2021-09-28T13:16:58Z | |
dc.date.created | 2021-07-01T14:13:11Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1664-302X | |
dc.identifier.uri | https://hdl.handle.net/11250/2784159 | |
dc.description.abstract | DNA 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.language.iso | eng | en_US |
dc.publisher | Frontiers | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Alleviation of C⋅C Mismatches in DNA by the Escherichia coli Fpg Protein | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.journal | Frontiers in Microbiology | en_US |
dc.identifier.doi | https://doi.org/10.3389/fmicb.2021.608839 | |
dc.identifier.cristin | 1919873 | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 |
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