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

被引：0

作者：

Pietro Fontana

Sara C. Buch-Larsen

Osamu Suyari

Rebecca Smith

Marcin J. Suskiewicz

Kira Schützenhofer

Antonio Ariza

Johannes Gregor Matthias Rack

Michael L. Nielsen

Ivan Ahel

机构：

[1] University of Oxford,Sir William Dunn School of Pathology

[2] South Parks Road,Department of Biological Chemistry and Molecular Pharmacology

[3] Harvard Medical School,Program in Cellular and Molecular Medicine

[4] Boston Children’s Hospital,Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences

[5] University of Copenhagen,undefined

[6] Blegdamsvej 3B,undefined

[7] Centre de Biophysique Moléculaire,undefined

[8] UPR4301 CNRS,undefined

[9] rue Charles Sadron,undefined

[10] CEDEX 2,undefined

[11] School of Biosciences,undefined

[12] University of Sheffield,undefined

[13] Western Bank,undefined

[14] MRC Centre for Medical Mycology,undefined

[15] School of Biosciences,undefined

[16] University of Exeter,undefined

[17] Geoffrey Pope Building,undefined

来源：

Nature Communications | / 14卷

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摘要：

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 dParp1:dHpf1 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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