Structural and functional characterization of two unusual endonuclease III enzymes from Deinococcus radiodurans

Succinylome Analysis Reveals the Involvement of Lysine Succinylation in the Extreme Resistance of Deinococcus radiodurans

“…Moreover, proteins involved in distinct DNA repair pathways were found to be succinylated. Both UvrB and Exonuclease III, which are the key components involved in nucleotide excision repair and base excision repair pathways, respectively, contained one succinylation site . The only extracellular nuclease in D. radiodurans was also succinylated at three sites .…”

A Decade of Biochemical and Structural Studies of the DNA Repair Machinery of Deinococcus radiodurans: Major Findings, Functional and Mechanistic Insight and Challenges

“…DNA glycosylases have been shown to stay tightly bound to their reaction products (typically abasic sites; reviewed in [124]), thereby preventing the generation of DSBs and maintaining the integrity of DNA, and thus facilitating its repair at a later stage. One of the three EndoIII variants of D. radiodurans , drEndoIII-3, displays no activity on classical EndoIII substrates but does bind tightly to oligonucleotides containing a stable abasic site [32]. The function of such an enzyme may be to protect damaged DNA rather than to repair it.…”

“…Structural studies have also been performed on several of these enzymes (Fig. 1) and at present crystal structures of drUNG (in absence and presence of DNA), drMUG, drAlkA2 and drEndoIII-1 and -3 have been determined [28], [29], [30], [31], [32].…”

“…The crystal structures of two of the three EndoIIIs (drEndoIII-1 and drEndoIII-3) were determined experimentally (Fig. 1), taking advantage of the [4Fe–4S] clusters in the enzymes, and a reliable homology model of the third member, drEndoIII-2, was generated using E. coli EndoIII (> 30% sequence identity) as a model [32]. DrEndoIII-3 had to be N-terminally truncated prior to crystallisation [47], but sequence analysis strongly indicates that the gene was most likely incorrectly annotated during the processing of the genome sequencing data [9].…”

“…Such measurements have indeed shown that drEndoIII-2 is a robust enzyme with strong bifunctional activity against the typical EndoIII substrate, thymine glycol (Tg), while drEndoIII-1 only exhibits weak glycosylase and lyase activities on Tg-containing DNA. In the case of drEndoIII-3, no enzymatic activity has so far been detected on common EndoIII substrates, even though the catalytic residues are conserved both in sequence and positioning in the structure [32]. At present, it is still unclear why D. radiodurans possesses these three EndoIII enzymes.…”