ArticleNucleic acids research2016
Analyzing structure-function relationships of artificial and cancer-associated PARP1 variants by reconstituting TALEN-generated HeLa PARP1 knock-out cells.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- LncRNA DANCR Regulates PARP1-Mediated Oxidative Stress Response in Corneas by Encoding a Novel Micropeptide miPEPDR.Investigative ophthalmology & visual science · 2026Article
- NAPRT-mediated deamidated NAD biosynthesis enhances colon tissue resiliency and suppresses tumorigenesis.Nature communications · 2026Article
- Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells.Nucleic acids research · 2025Article
- A Population-Specific PARP1 Gene Variation Modulates PARP Trapping.bioRxiv : the preprint server for biology · 2025Article
- Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer.Future medicinal chemistry · 2025Article
- Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM.Nature communications · 2024Article
- DNA damage-induced EMT controlled by the PARP-dependent chromatin remodeler ALC1 promotes DNA repair efficiency through RAD51 in tumor cells.Molecular biology of the cell · 2024Article
- Phase Separation of FUS with Poly(ADP-ribosyl)ated PARP1 Is Controlled by Polyamines, Divalent Metal Cations, and Poly(ADP-ribose) Structure.International journal of molecular sciences · 2024Article
- Monitoring nucleolar-nucleoplasmic protein shuttling in living cells by high-content microscopy and automated image analysis.Nucleic acids research · 2024Article
- PARP1-dependent DNA-protein crosslink repair.Nature communications · 2024Article
- AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- PARP1 bound to XRCC2 promotes tumor progression in colorectal cancer.Discover oncology · 2024Article
- Article
- NADCells · 2023Article
- PARP1 and XRCC1 exhibit a reciprocal relationship in genotoxic stress response.Cell biology and toxicology · 2023Article
- Mitochondrial PARP1 regulates NADExperimental & molecular medicine · 2022Article
- Fueling genome maintenance: On the versatile roles of NADThe Journal of biological chemistry · 2022Review
- Why structure and chain length matter: on the biological significance underlying the structural heterogeneity of poly(ADP-ribose).Nucleic acids research · 2021Article
- PARP1 catalytic variants reveal branching and chain length-specific functions of poly(ADP-ribose) in cellular physiology and stress response.Nucleic acids research · 2020Article
- Clinical PARP inhibitors do not abrogate PARP1 exchange at DNA damage sites in vivo.Nucleic acids research · 2020Article
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20 authors.
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Abstract
Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure-function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\L713F mutant is constitutively active in cells. Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser-induced DNA damage, which can potentially be attributed to non-covalent PARP1-PAR interaction via several PAR binding motifs. Thirdly, both mutants had distinct functional consequences in cellular patho-physiology, i.e. PARP1\L713F expression triggered apoptosis, whereas PARP1\E988K reconstitution caused a DNA-damage-induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor treatment, indicating distinct cellular consequences of constitutive PARylation and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation (F304L\V762A) present in a patient with pediatric colorectal carcinoma exhibit altered biochemical and cellular properties, thereby potentially supporting human carcinogenesis. Together, we establish a novel cellular model for PARylation research, by revealing strong structure-function relationships of natural and artificial PARP1 variants.
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