Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling - Aspects Moléculaires du Vivant
Article Dans Une Revue Nature Communications Année : 2023

Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling

Pietro Fontana
Sara C Buch-Larsen
Osamu Suyari
Rebecca Smith
Kira Schützenhofer
  • Fonction : Auteur
Antonio Ariza
Johannes Gregor Matthias Rack
Michael L Nielsen
Ivan Ahel
  • Fonction : Auteur
  • PersonId : 1104766

Résumé

In the mammalian DNA damage response, ADP-ribosylation signalling is of crucial importance to mark sites of DNA damage as well as recruit and regulate repairs factors. Specifically, the PARP1:HPF1 complex recognises damaged DNA and catalyses the formation of serine-linked ADP-ribosylation marks (mono-Ser-ADPr), which are extended into ADP-ribose polymers (poly-Ser-ADPr) by PARP1 alone. Poly-Ser-ADPr is reversed by PARG, while the terminal mono-Ser-ADPr is removed by ARH3. Despite its significance and apparent evolutionary conservation, little is known about ADP-ribosylation signalling in non-mammalian Animalia . The presence of HPF1, but absence of ARH3, in some insect genomes, including Drosophila species, raises questions regarding the existence and reversal of serine-ADP-ribosylation in these species. Here we show by quantitative proteomics that Ser-ADPr is the major form of ADP-ribosylation in the DNA damage response of Drosophila melanogaster and is dependent on the d Parp1: d Hpf1 complex. Moreover, our structural and biochemical investigations uncover the mechanism of mono-Ser-ADPr removal by Drosophila Parg. Collectively, our data reveal PARP:HPF1-mediated Ser-ADPr as a defining feature of the DDR in Animalia . The striking conservation within this kingdom suggests that organisms that carry only a core set of ADP-ribosyl metabolising enzymes, such as Drosophila , are valuable model organisms to study the physiological role of Ser-ADPr signalling.
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Dates et versions

hal-04127612 , version 1 (13-06-2023)

Identifiants

Citer

Pietro Fontana, Sara C Buch-Larsen, Osamu Suyari, Rebecca Smith, Marcin J Suskiewicz, et al.. Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling. Nature Communications, 2023, 14 (1), pp.3200. ⟨10.1038/s41467-023-38793-y⟩. ⟨hal-04127612⟩
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