DR0022 from Deinococcus radiodurans is an acid uracil‐DNA glycosylase

Abstract

Uracil‐DNA glycosylase (UDG) initiates base excision repair (BER) by removing damaged or modified nucleobases during DNA repair or mammalian demethylation. The UDG superfamily consists of at least six families with a variety of catalytic specificities and functions. Deinococcus radiodurans, an extreme radiation resistant bacterium, contains multiple members of UDG enzymes within its genome. The present study reveals that the putative protein, DR0022, is a uracil‐DNA glycosylase that requires acidic conditions for its glycosylase activity, which is the first case of such an enzyme within the UDG superfamily. The key residues in the catalytic motifs are investigated by biochemical, enzyme kinetics, and de novo structural prediction, as well as molecular modeling analyses. The structural and catalytic roles of several distinct residues are discussed in light of predicted and modeled DR0022 glycosylase structures. The spontaneous mutation rate analysis performed in a dr0022 deficient D. radiodurans strain indicated that the dr0022 gene plays a role in mutation prevention. Furthermore, survival rate analysis in a dr0022 deficient D. radiodurans strain demonstrated its role in stress resistance, including γ‐irradiation. Additionally, the novel acid UDG activity in relationship to its in vivo roles is discussed. This work underscores the functional diversity in the UDG superfamily.

DNA repair and oxidative stress defense systems in radiation-resistant Deinococcus murrayi

“…DNA repair proteins encoded by D. murrayi are listed in Table 1. Because most studies concerning deinococcal DNA repair have been performed with genes and proteins from D. radiodurans (Lim et al 2019;Cheng et al 2020;He et al 2020;Kota et al 2021;Ujaoney et al 2021;Jeong et al 2021b;Li et al 2022;Sun et al 2022;Seck et al 2023;Yang et al 2023) (and references therein), the gene locus tags of this species are included. For every protein from D. murrayi and/or D. radiodurans, Table 1 also lists the number of homologs in 10 other previously analyzed Deinococcus species (Lim et al 2019).…”