title: Catalytic and non-catalytic roles for the mono-ADP-ribosyltransferase Arr in the mycobacterial DNA damage response.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Stallings
authors.forename: Linda
authors.initials: L
authors.lastname: Chu
authors.forename: Lucy X
authors.initials: LX
authors.lastname: Li
authors.forename: Michael S
authors.initials: MS
authors.lastname: Glickman
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D055162:Biocatalysis / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial / Q000235:genetics; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D012335:RNA, Ribosomal / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D013312:Stress, Physiological / Q000235:genetics; D013379:Substrate Specificity / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D036002:ADP Ribose Transferases; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin