Novel Sequence Features of DNA Repair Genes/Proteins from Deinococcus Species Implicated in Protection from Oxidatively Generated Damage

Abstract

<i>Deinococcus</i> species display a high degree of resistance to radiation and desiccation due to their ability to protect critical proteome from oxidatively generated damage; however, the underlying mechanisms are not understood. Comparative analysis of DNA repair proteins reported here has identified 22 conserved signature indels (CSIs) in the proteins UvrA1, UvrC, UvrD, UvsE, MutY, MutM, Nth, RecA, RecD, RecG, RecQ, RecR, RuvC, RadA, PolA, DnaE, LigA, GyrA and GyrB, that are uniquely shared by all/most <i>Deinococcus</i> homologs. Of these CSIs, a 30 amino acid surface-exposed insert in the <i>Deinococcus</i> UvrA1, which distinguishes it from all other UvrA homologs, is of much interest. The <i>uvrA1</i> gene in <i>Deinococcus</i> also exhibits specific genetic linkage (predicted operonic arrangement) to genes for three other proteins including a novel <i>Deinococcus</i>-specific transmembrane protein (designated dCSP-1) and the proteins DsbA and DsbB, playing central roles in protein disulfide bond formation by oxidation-reduction of CXXC (C represents cysteine, X any other amino acid) motifs. The CXXC motifs provide important targets for oxidation damage and they are present in many DNA repair proteins including five in UvrA, which are part of Zinc-finger elements. A conserved insert specific for <i>Deinococcus</i> is also present in the DsbA protein. Additionally, the <i>uvsE</i> gene in <i>Deinococcus</i> also shows specific linkage to the gene for a membrane-associated protein. To account for these novel observations, a model is proposed where specific interaction of the <i>Deinococcus</i> UvrA1 protein with membrane-bound dCSP-1 enables the UvrA1 to receive electrons from DsbA-DsbB oxido-reductase machinery to ameliorate oxidation damage in the UvrA1 protein.