Catalytic and non-catalytic roles for the mono-ADP-ribosyltransferase Arr in the mycobacterial DNA damage response

• Published in: PloS one 2011-07, Vol.6 (7), p.e21807
• Main Authors: Stallings, Christina L, Chu, Linda, Li, Lucy X, Glickman, Michael S
• Format: Article
• Language: English
• Subjects: Acinetobacter; Adenosine diphosphate; ADP Ribose Transferases - genetics; ADP Ribose Transferases - metabolism; Bacillus subtilis; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biocatalysis - drug effects; Biology; Catalysis; Catalytic activity; Cellular stress response; Damage detection; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded - drug effects; DNA damage; DNA Damage - genetics; DNA repair; DNA Repair - genetics; DNA-Directed RNA Polymerases - metabolism; Drug Resistance, Bacterial - drug effects; Drug Resistance, Bacterial - genetics; E coli; Escherichia coli; Experiments; Gene expression; Gene Expression Regulation, Bacterial - drug effects; Genes; Genes, Bacterial - genetics; Genomes; Immunology; Klebsiella pneumoniae; Leprosy; Medicine; Mycobacterium smegmatis - drug effects; Mycobacterium smegmatis - enzymology; Mycobacterium smegmatis - genetics; Mycobacterium tuberculosis; Non-homologous end joining; Oligonucleotide Array Sequence Analysis; Protein Binding; Proteins; Pseudomonas aeruginosa; Repair; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; Rifampin; Rifampin - pharmacology; RNA; RNA polymerase; RNA, Ribosomal - metabolism; rRNA; Stress, Physiological - genetics; Substrate Specificity - drug effects; Transcription; Transcription (Genetics); Trends; Tuberculosis; Ultraviolet radiation; Up-Regulation - drug effects; Up-Regulation - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0021807

Recent evidence indicates that the mycobacterial response to DNA double strand breaks (DSBs) differs substantially from previously characterized bacteria. These differences include the use of three DSB repair pathways (HR, NHEJ, SSA), and the CarD pathway, which integrates DNA damage with transcription. Here we identify a role for the mono-ADP-ribosyltransferase Arr in the mycobacterial DNA damage response. Arr is transcriptionally induced following DNA damage and cellular stress. Although Arr is not required for induction of a core set of DNA repair genes, Arr is necessary for suppression of a set of ribosomal protein genes and rRNA during DNA damage, placing Arr in a similar pathway as CarD. Surprisingly, the catalytic activity of Arr is not required for this function, as catalytically inactive Arr was still able to suppress ribosomal protein and rRNA expression during DNA damage. In contrast, Arr substrate binding and catalytic activities were required for regulation of a small subset of other DNA damage responsive genes, indicating that Arr has both catalytic and noncatalytic roles in the DNA damage response. Our findings establish an endogenous cellular function for a mono-ADP-ribosyltransferase apart from its role in mediating Rifampin resistance.