ArticleeLife2021
HPF1 and nucleosomes mediate a dramatic switch in activity of PARP1 from polymerase to hydrolase.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- DNA-PKcs and PARP1 at the interface between DNA damage responses and cGAS-STING signaling: context-dependent roles and therapeutic implications.Cancer biology & therapy · 2026Review
- PARP1 Exhibits an Enzymatically Inactive Chromatin Binding Mode.bioRxiv : the preprint server for biology · 2026Article
- Deciphering cytokine-driven ADP-ribosylation signaling networks via Af1521-based mass spectrometry analysis of labile Glu/Asp-linkages.Nature communications · 2026Article
- Simultaneous Detection and Quantification of Adenine Nucleotides in Mammalian Cultured Cells by HPLC.ACS omega · 2026Article
- HPF1 regulates the formation of FUS-dependent compartments by PARP1 and PARP2 activation on damaged DNA.Nucleic acids research · 2026Article
- Nucleosome unwrapping and PARP1 allostery drive affinities for chromatin and DNA breaks.Nature communications · 2025Article
- Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.Journal of Huntington's disease · 2025Review
- Histone PARylation factor 1: a review of its role in the DNA damage response.Nucleic acids research · 2025Review
- PARP enzyme synthesis of protein-free poly(ADP-ribose): Implications for DNA damage signaling and repair.DNA repair · 2025Review
- Deciphering the dark side of histone ADP-ribosylation: what structural features of damaged nucleosome regulate the activities of PARP1 and PARP2.Nucleic acids research · 2025Article
- HPF1 Regulates Pol β Efficiency in Nucleosomes via the Modulation of Total Poly(ADP-Ribose) Synthesis.International journal of molecular sciences · 2025Article
- PARP enzyme de novo synthesis of protein-free poly(ADP-ribose).Molecular cell · 2024Article
- PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation.EMBO reports · 2024Article
- Aminomethylmorpholino Nucleosides as Novel Inhibitors of PARP1 and PARP2: Experimental and Molecular Modeling Analyses of Their Selectivity and Mechanism of Action.International journal of molecular sciences · 2024Article
- Dispensability of HPF1 for cellular removal of DNA single-strand breaks.Nucleic acids research · 2024Article
- Histone ADP-ribosylation promotes resistance to PARP inhibitors by facilitating PARP1 release from DNA lesions.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Cooperative nucleic acid binding by Poly ADP-ribose polymerase 1.Scientific reports · 2024Article
- MiR-203 improves cardiac dysfunction by targeting PARP1-NADAging cell · 2024Article
- Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1.Nature communications · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Poly(ADP-ribose) polymerase 1 (PARP1) is an important player in the response to DNA damage. Recently, Histone PARylation Factor (HPF1) was shown to be a critical modulator of the activity of PARP1 by facilitating PARylation of histones and redirecting the target amino acid specificity from acidic to serine residues. Here, we investigate the mechanism and specific consequences of HPF1-mediated PARylation using nucleosomes as both activators and substrates for PARP1. HPF1 provides that catalytic base Glu284 to substantially redirect PARylation by PARP1 such that the histones in nucleosomes become the primary recipients of PAR chains. Surprisingly, HPF1 partitions most of the reaction product to free ADP-ribose (ADPR), resulting in much shorter PAR chains compared to reactions in the absence of HPF1. This HPF1-mediated switch from polymerase to hydrolase has important implications for the PARP1-mediated response to DNA damage and raises interesting new questions about the role of intracellular ADPR and depletion of NAD
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.