PprA contributes to Deinococcus radiodurans resistance to nalidixic acid, genome maintenance after DNA damage and interacts with deinococcal topoisomerases

• Published in: PloS one Vol. 9; no. 1; p. e85288
• Main Authors: Kota, Swathi, Charaka, Vijaya K, Ringgaard, Simon, Waldor, Matthew K, Misra, Hari S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-01-2014; Public Library of Science (PLoS)
• Subjects: Acid resistance; Acids; Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - physiology; Base Sequence; Biology; Cell division; Damage; Deinococcus - drug effects; Deinococcus - genetics; Deinococcus - physiology; Deinococcus radiodurans; Deoxyribonucleic acid; DNA; DNA Damage; DNA Primers; DNA repair; DNA topoisomerase (ATP-hydrolysing); DNA Topoisomerases, Type I - metabolism; Double-strand break repair; Drug Resistance, Bacterial - genetics; E coli; Enzymes; Escherichia coli; Gene expression; Genome, Bacterial; Genomes; Genomics; Genotoxicity; Infectious diseases; Ionizing radiation; Kinases; Laboratories; Ligases; Medical schools; Molecular biology; Nalidixic acid; Nalidixic Acid - pharmacology; Plasmids; Proteins; Repair; Reverse Transcriptase Polymerase Chain Reaction; Signal transduction; Womens health; Mumbai India; United States > US; Massachusetts; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085288

PprA is known to contribute to Deinococcus radiodurans' remarkable capacity to survive a variety of genotoxic assaults. The molecular bases for PprA's role(s) in the maintenance of the damaged D. radiodurans genome are incompletely understood, but PprA is thought to promote D. radiodurans's capacity for DSB repair. PprA is found in a multiprotein DNA processing complex along with an ATP type DNA ligase, and the D. radiodurans toposiomerase IB (DraTopoIB) as well as other proteins. Here, we show that PprA is a key contributor to D. radiodurans resistance to nalidixic acid (Nal), an inhibitor of topoisomerase II. Growth of wild type D. radiodurans and a pprA mutant were similar in the absence of exogenous genotoxic insults; however, the pprA mutant exhibited marked growth delay and a higher frequency of anucleate cells following treatment with DNA-damaging agents. We show that PprA interacts with both DraTopoIB and the Gyrase A subunit (DraGyrA) in vivo and that purified PprA enhances DraTopoIB catalysed relaxation of supercoiled DNA. Thus, besides promoting DNA repair, our findings suggest that PprA also contributes to preserving the integrity of the D. radiodurans genome following DNA damage by interacting with DNA topoisomerases and by facilitating the actions of DraTopoIB.