ArticleCancer research2019
Phosphatase 1 Nuclear Targeting Subunit Mediates Recruitment and Function of Poly (ADP-Ribose) Polymerase 1 in DNA Repair.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Transcriptome-wide association study of alternative polyadenylation identifies susceptibility genes in non-small cell lung cancer.Oncogene · 2025Article
- PNUTS:PP1 recruitment to Tox4 regulates chromosomal dispersal in Drosophila germline development.Cell reports · 2025Article
- Protein Phosphatase 1 Regulatory Subunit PNUTS Prevents CENP-A Mislocalization and Chromosomal Instability.Molecular and cellular biology · 2025Article
- Development of Drug-Induced Gene Expression Ranking Analysis (DIGERA) and Its Application to Virtual Screening for Poly (ADP-Ribose) Polymerase 1 Inhibitor.International journal of molecular sciences · 2024Article
- The PNUTS phosphatase complex controls transcription pause release.Molecular cell · 2024Article
- Article
- PINX1 loss confers susceptibility to PARP inhibition in pan-cancer cells.Cell death & disease · 2024Article
- Human PARP1 substrates and regulators of its catalytic activity: An updated overview.Frontiers in pharmacology · 2023Review
- PARP1-modulated chromatin remodeling is a new target for cancer treatment.Medical oncology (Northwood, London, England) · 2021Review
- PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance.Frontiers in cell and developmental biology · 2021Article
- KRCC1: A potential therapeutic target in ovarian cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Poly(ADP-Ribose)Polymerase (PARP) Inhibitors and Radiation Therapy.Frontiers in pharmacology · 2020Review
- Upregulation of Phosphatase 1 Nuclear-Targeting Subunit (PNUTS) Is an Independent Predictor of Poor Prognosis in Prostate Cancer.Disease markers · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
PARP, particularly PARP1, plays an essential role in the detection and repair of DNA single-strand breaks and double-strand breaks. PARP1 accumulates at DNA damage sites within seconds after DNA damage to catalyze the massive induction of substrate protein poly ADP-ribosylation (PARylation). However, the molecular mechanisms underlying the recruitment and activation of PARP1 in DNA repair are not fully understood. Here we show that phosphatase 1 nuclear targeting subunit 1 (PNUTS) is a robust binding partner of PARP1. Inhibition of PNUTS led to strong accumulation of endogenous DNA damage and sensitized the cellular response to a wide range of DNA-damaging agents, implicating PNUTS as an essential and multifaceted regulator of DNA repair. Recruitment of PNUTS to laser-induced DNA damage was similar to that of PARP1, and depletion or inhibition of PARP1 abrogated recruitment of PNUTS to sites of DNA damage. Conversely, PNUTS was required for efficient induction of substrate PARylation after DNA damage. PNUTS bound the BRCA1 C-terminal (BRCT) domain of PARP1 and was required for the recruitment of PARP1 to sites of DNA damage. Finally, depletion of PNUTS rendered cancer cells hypersensitive to PARP inhibition. Taken together, our study characterizes PNUTS as an essential partner of PARP1 in DNA repair and a potential drug target in cancer therapy. SIGNIFICANCE: These findings reveal PNUTS as an essential functional partner of PARP1 in DNA repair and suggest its inhibition as a potential therapeutic strategy in conjunction with DNA-damaging agents or PARP inhibitors.
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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.