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

Christina L. Stallings, Linda Chu, Lucy X. Li, Michael S. Glickman

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish
Article numbere21807
JournalPloS one
Volume6
Issue number7
DOIs
StatePublished - Jul 26 2011

Fingerprint Dive into the research topics of 'Catalytic and non-catalytic roles for the mono-ADP-ribosyltransferase arr in the mycobacterial DNA damage response'. Together they form a unique fingerprint.

  • Cite this