Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling

Longarini, E.J.; Dauben, H.; Locatelli, C.; Wondisford, A.R.; Smith, R.; Muench, C.; Kolvenbach, A.; Lynskey, M.L.; Pope, A.; Bonfiglio, J.J.; Jurado, E.P.; Fajka-Boja, R. [Fajka-Boja, Roberta (Molekuláris és se...), szerző] Genetikai Intézet (HRN SZBK); Immunológiai Tanszék (SZTE / SZAOK); Immunológiai Tanszék (SZTE / TTIK / BI); Colby, T.; Schuller, M.; Ahel, I.; Timinszky, G. [Timinszky, Gyula (kromatin), szerző] Genetikai Intézet (HRN SZBK); O'Sullivan, R.J.; Huet, S. ✉; Matic, I. ✉

Angol nyelvű Szakcikk (Folyóiratcikk) Tudományos
Megjelent: MOLECULAR CELL 1097-2765 1097-4164 83 (10) pp. 1743-1760.e11 2023
  • SJR Scopus - Cell Biology: D1
Azonosítók
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)
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
2024-11-06 16:34