Serine ADP-ribosylation depends on HPF1
Open accessAbstract
ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. However, the biochemical basis underlying this serine modification remained unknown. Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. Quantitative proteomics revealed that serine ADPr does not occur in cells lacking HPF1. Moreover, adding HPF1 to in vitro PARP-1/PARP-2 reactions is necessary and sufficient for serine-specific ADPr of histones and PARP-1 itself. Three endogenous serine ADPr sites are located on the PARP-1 automodification domain. Further identification of serine ADPr on HMG proteins and hundreds of other targets indicates that serine ADPr is a widespread modification. We propose that O-linked protein ADPr is the key signal in PARP-1/PARP-2-dependent processes that govern genome stability.
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PARP1 transfers the first ADP-ribose moiety from NAD+ to specific residues on an acceptor protein and then adds multiple ADP-ribose units to form PAR chains.
“Experimental evidence supports that PARP1 transfers the first ADP-ribose moiety from NAD+ to lysine, arginine, glutamate, aspartate, and serine residues on an acceptor protein, followed by addition of multiple ADP-ribose units to the preceding ones, thereby forming poly(ADP-ribose) (PAR) chains (Bonfiglio et al., 2017; Daniels et al., 2014).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Bonfiglio et al., 2017
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References 48 · Cited by 352
- Authors
- Bonfiglio, J. J., Fontana, P., Zhang, Q., Colby, T., Gibbs-Seymour, I., Atanassov, I., Bartlett, E., Zaja, R., Ahel, I., & Matic, I.
- Affiliations
- University of Oxford (GB)
- Max Planck Institute for Biology of Ageing (DE)
- Corresponding author
- Ahel, Ivan
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 65
- Issue
- 5
- Pages
- 932-940.e6
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5344681
- OpenAlex
- W2587003776
- Cited by
- 352
- References
- 48
- Citations by year
- 2026: 34 · 2025: 37 · 2024: 47 · 2023: 40 · 2022: 34 · 2021: 49 · 2020: 33 · 2019: 32 · 2018: 29 · 2017: 17
- FWCI
- 13.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (EXC 229)
- European Union’s Horizon 2020 (657501)
- Wellcome Trust (101794)
- Cancer Research UK (C35050/A22284)
- European Research Council (281739)
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- HPF1, PARP1, PARP2, DNA damage response, histone modifications, high mobility group proteins, genome stability
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Adenosine Diphosphate Ribose, Carrier Proteins, Histones, Humans, Nuclear Proteins, Poly(ADP-ribose) Polymerases, Protein Processing, Post-Translational, Serine, Transfection, Proteomics, Genomic Instability, Cell Line, Tumor
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