Title Alleviation of C⋅C mismatches in DNA by the Escherichia coli Fpg protein /
Authors Tesfahun, Almaz Nigatu ; Alexeeva, Marina ; Tomkuvienė, Miglė ; Arshad, Aysha ; Guragain, Prashanna ; Klungland, Arne ; Klimašauskas, Saulius ; Ruoff, Peter ; Bjelland, Svein
DOI 10.3389/fmicb.2021.608839
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Is Part of Frontiers in microbiology.. Lausanne : Frontiers media SA. 2021, vol. 12, art. no. 608839, p. [1-10].. eISSN 1664-302X
Keywords [eng] DNA base mismatch ; DNA glycosylase ; Escherichia coli Fpg ; base excision repair ; cytosine:cytosine mismatch ; mutM ; thymine:thymine mismatch
Abstract [eng] 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 k cat 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 K M 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 N 4- 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.
Published Lausanne : Frontiers media SA
Type Journal article
Language English
Publication date 2021
CC license CC license description