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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.
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Kolvenbach, A.
;
Lynskey, M.L.
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Pope, A.
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Bonfiglio, J.J.
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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)
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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
MTMT: 34002643
DOI:
10.1016/j.molcel.2023.03.027
WoS:
001001880200001
REAL:
174998
Scopus:
85159185641
PubMed:
37116497
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)
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2024-11-06 16:34
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