PolyADP-ribosylation articles from across Nature Portfolio

Thioredoxin 1 (TrxA) is an enzyme that reduces disulfide bonds in the bacterial cytosol. Here, the AUs show that TrxA can function as a chaperone of the secreted bacterial ADP-ribosyltransferase toxin TreX independent of redox catalysis.

The role of PARylation, a modification with NAD⁺ as substrate, in Magnaporthe oryzae virulence is investigated. MoPARP1-mediated PARylation of 14-3-3 proteins is found to be required for activation of Pmk1, the key mitogen-activated kinase dictating appressorium development and virulence.

Here the authors reveal a two-step spatiotemporal regulation of (Polθ)-mediated end-joining (TMEJ). First, PARP1 PARylates Polθ and facilitates its recruitment to the vicinity of DNA damage sites in an inactivated state. PARG subsequently activates TMEJ by removing repressive PAR marks on Polθ.

Ester-linked modifications are common but difficult to detect. Here, the authors present methods based on ester preservation and a sensitive antibody to reveal DNA damage-induced mono-ADP-ribosylation on aspartate and glutamate. This signal, part of the first wave of PARP1 signaling, is removed by PARG.

Telomeres are endogenous cellular targets of DNA ADP-ribosylation (DNA-ADPr). TARG1-regulated DNA-ADPr is coupled to lagging telomere DNA strand synthesis, and persistent DNA-ADPr, due to TARG1 deficiency, leads to telomere shortening and fragility.

ADP-ribosylation regulates the activity of numerous proteins involved in the DNA damage response and repair. A new study shows that telomeric DNA can be ADP-ribosylated by PARP1, and prompt removal of the ADP-ribose by TARG1 is essential to preserve telomere integrity, unveiling DNA–ADP-ribosylation as a novel player in telomere stability.

García Saura et al. report a new tool, MacroGreen, to detect ADP-ribosylation by GFP fluorescence in a microplate reader, or in cells by microscopy. With superior affinity and reduced ADP-ribosyl hydrolase activity, MacroGreen is an easy to produce and suitable tool for rapid detection of ADP-ribosylated proteins in vitro without a need for specialist reagents and time-consuming methods.

The use of a chemical genetics approach to identify poly(ADP-ribose) polymerase (PARP) targets revealed that PARP1 promotes transcription elongation.

Macrodomains are conserved globular domains that can interact with, and in some cases modify, ADP-ribose–based molecules. In this issue, two reports add to the functional repertoire of this domain, by demonstrating that a subset of macrodomain-containing proteins functions to catalyze the removal of protein-proximal ADP-ribose.