4.5 Review

Beyond protein modification: the rise of non-canonical ADP-ribosylation

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Summary: ADP-ribosylation, a post-translational modification of proteins, nucleic acids, and metabolites, plays diverse roles in cellular processes such as stress responses, signaling, and transcriptional regulation. Recent advances in research have identified a wide range of cellular pathways regulated by ADP-ribosylation, highlighting the importance of understanding this mechanism in cell biology.

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Summary: Despite years of research on ADP-ribosyltransferases from the PARP family, their substrate specificity has remained unclear. Recent breakthroughs include identifying protein serine residues, cysteine, and tyrosine as potential targets of specific PARPs. These findings shed new light on PARP-mediated catalysis and caution to expect the unexpected with potential substrates.

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Serine ADP-ribosylation in DNA-damage response regulation

Luca Palazzo et al.

Summary: PARP1 and PARP2 regulate DNA damage response by catalyzing reversible post-translational modification ADPribosylation. Serine ADP-ribosylation at damage sites leads to recruitment of repair factors for efficient DNA repair. Tight control of ADPribosylation signaling by (ADP-ribosyl)glycohydrolases ensures proper kinetics of DNA repair and cell cycle re-entry, providing new insights into human physiopathology and cancer therapy.

CURRENT OPINION IN GENETICS & DEVELOPMENT (2021)

Article Multidisciplinary Sciences

Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11

Zilin Li et al.

Summary: This study identified a novel post-translational modification, ADP riboxanation, mediated by the Shigella effector OspC3, which inactivates the LPS sensing pathway of caspase-4 and caspase-11 and prevents pyroptosis. ADP riboxanation modification on Arg314 and Arg310 in caspase-4 and caspase-11 inhibits their activity, leading to evasion of host defense against Shigella infection. This bacterial virulence mechanism highlights the importance of ADP riboxanation in preventing LPS-induced pyroptosis.

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The regulatory landscape of the human HPF1-and ARH3-dependent ADP-ribosylome

Ivo A. Hendriks et al.

Summary: By utilizing quantitative proteomics, the authors identified 1,596 ADP-ribosylation sites and found that HPF1 and ARH3 regulate serine ADP-ribosylation in an inverse and homogeneous manner on a proteome-wide scale. This regulation is consistent with lysine-serine motifs, indicating independence from HPF1 and ARH3.

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Sridevi Challa et al.

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ADP-ribosylation of DNA and RNA

Josephine Groslambert et al.

Summary: ADP-ribosylation is a reversible chemical modification found in all domains of life, playing important roles in DNA damage response. It can target not only proteins but also nucleic acids such as DNA bases, phosphorylated DNA and RNA ends. These discoveries have led to the emergence of a new research area focusing on DNA and RNA ADP-ribosylation, likely to have significant implications for DNA repair, replication, and epigenetics.

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Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease

Evgeniia Prokhorova et al.

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Molecular basis for DarT ADP-ribosylation of a DNA base

Marion Schuller et al.

Summary: ADP-ribosyltransferases use NAD(+) to catalyze substrate ADP-ribosylation and regulate cellular pathways or contribute to bacterial pathogenicity. Recent studies have suggested nucleic acids as targets of reversible ADP-ribosylation. This research provides evidence of specific ADP-ribosylation of DNA in cells through the DarT-DarG system in bacteria, including global pathogens. The study reveals the structure and mechanism of the DarT enzyme, showing its evolution into specific DNA-modifying enzymes and its role in regulating growth through DNA ADP-ribosylation.

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Callum Tromans-Coia et al.

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Summary: Poly(ADP-ribosyl)ation is a versatile posttranslational modification involved in regulating cellular processes. This study focuses on the mechanisms of PAR removal by PARG and ARH3, highlighting their differences in hydrolysis of linear and terminal ADP-ribose linkages.

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ADP-ribosylation systems in bacteria and viruses

Petra Mikolcevic et al.

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HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation

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