Longarini, Edoardo Jose and Dauben, Helen and Locatelli, Carolina and Wondisford, Anne R. and Smith, Rebecca and Muench, Charlotte and Kolvenbach, Andreas and Lynskey, Michelle Lee and Pope, Alexis and Bonfiglio, Juan Jose and Jurado, Eva Pinto and Fajka-Boja, Roberta and Colby, Thomas and Schuller, Marion and Ahel, Ivan and Timinszky, Gyula and O’Sullivan, Roderick J. and Huet, Sebastien and Matic, Ivan (2023) Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling. MOLECULAR CELL, 83 (10). 1743-1760.e11. ISSN 1097-2765
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Abstract
PARP1, an established anti-cancer target that regulates many cellular pathways, including DNA repair signaling, has been intensely studied for decades as a poly(ADP-ribosyl)transferase. Although recent studies have revealed the prevalence of mono-ADP-ribosylation upon DNA damage, it was unknown whether this signal plays an active role in the cell or is just a byproduct of poly-ADP-ribosylation. By engineering SpyTag-based modular antibodies for sensitive and flexible detection of mono-ADP-ribosylation, including fluorescence-based sensors for live-cell imaging, we demonstrate that serine mono-ADP-ribosylation constitutes a second wave of PARP1 signaling shaped by the cellular HPF1/PARP1 ratio. Multilevel chromatin proteomics reveals histone mono-ADP-ribosylation readers, including RNF114, a ubiquitin ligase recruited to DNA lesions through a zinc-finger domain, modulating the DNA damage response and telomere maintenance. Our work provides a technological framework for illuminating ADP-ribosylation in a wide range of applications and biological contexts and establishes mono-ADP-ribosylation by HPF1/PARP1 as an important information carrier for cell signaling. © 2023 The Author(s)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | metabolism; GENETICS; ANTIBODIES; ANTIBODIES; signal transduction; signal transduction; ANTIBODY; Chromatin; Chromatin; DNA Damage; DNA Damage; Histone; telomere; Histones; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; ADP-RIBOSYLATION; ADP-RIBOSYLATION; adenosine diphosphate ribosylation; PARP1; DNA damage response; Poly (ADP-ribose) polymerase-1; HPF1; RNF114; SpyTag |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 26 Sep 2023 11:15 |
| Last Modified: | 26 Sep 2023 11:15 |
| URI: | http://real.mtak.hu/id/eprint/174998 |
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