The three Endonuclease III variants of Deinococcus radiodurans possess distinct and complementary DNA repair activities

Aili Sarre, Meike Stelter, Filipe Rollo, Salvatore De Bonis, Anna Seck, Cécilia Hognon, Jean Luc Ravanat, Antonio Monari, François Dehez, Elin Moe, Joanna Timmins

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Endonuclease III (EndoIII) is a bifunctional DNA glycosylase that removes oxidized pyrimidines from DNA. The genome of Deinococcus radiodurans encodes for an unusually high number of DNA glycosylases, including three EndoIII enzymes (drEndoIII1-3). Here, we compare the properties of these enzymes to those of their well-studied homologues from E. coli and human. Our biochemical and mutational data, reinforced by MD simulations of EndoIII-DNA complexes, reveal that drEndoIII2 exhibits a broad substrate specificity and a catalytic efficiency surpassing that of its counterparts. In contrast, drEndoIII1 has much weaker and uncoupled DNA glycosylase and AP-lyase activities, a characteristic feature of eukaryotic DNA glycosylases, and was found to present a relatively robust activity on single-stranded DNA substrates. To our knowledge, this is the first report of such an activity for an EndoIII. In the case of drEndoIII3, no catalytic activity could be detected, but its ability to specifically recognize lesion-containing DNA using a largely rearranged substrate binding pocket suggests that it may play an alternative role in genome maintenance. Overall, these findings reveal that D. radiodurans possesses a unique set of DNA repair enzymes, including three non-redundant EndoIII variants with distinct properties and complementary activities, which together contribute to genome maintenance in this bacterium.

Original languageEnglish
Pages (from-to)45-59
Number of pages15
JournalDNA Repair
Volume78
DOIs
Publication statusPublished - 1 Jun 2019

Keywords

  • Base excision repair
  • Catalytic activity
  • Deinococcus radiodurans
  • DNA glycosylase
  • Endonuclease III
  • Oxidative DNA damage
  • Radiation resistance

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