ArticleMolecular and cellular biology2015
Poly(ADP-ribosyl) glycohydrolase prevents the accumulation of unusual replication structures during unperturbed S phase.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- PARG inhibition reduces ssDNA levels and limits RPA loading upon replication fork collapse.EMBO reports · 2026Article
- FET proteins and PARylation-dependent condensates promote replication fork reversal and genome stability.Nature communications · 2026Article
- Article
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis.NAR cancer · 2025Article
- Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels.Nature communications · 2025Article
- Poly (ADP-Ribose) Glycohydrolase-Dependent dePARylation of PCNA Is Essential for DNA Replication.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Prospects for PARG inhibitors in cancer therapy.Journal of molecular cell biology · 2025Review
- PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- PARG-deficient tumor cells have an increased dependence on EXO1/FEN1-mediated DNA repair.The EMBO journal · 2024Article
- Targeting OGG1 and PARG radiosensitises head and neck cancer cells to high-LET protons through complex DNA damage persistence.Cell death & disease · 2024Article
- Multiple-low-dose therapy: effective killing of high-grade serous ovarian cancer cells with ATR and CHK1 inhibitors.NAR cancer · 2022Article
- The disruption of the CCDC6 - PP4 axis induces a BRCAness like phenotype and sensitivity to PARP inhibitors in high-grade serous ovarian carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- The expanding universe of PARP1-mediated molecular and therapeutic mechanisms.Molecular cell · 2022Review
- p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways.Cell death and differentiation · 2022Review
- Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease.Molecular cell · 2021Article
- Combined Targeting of PARG and Wee1 Causes Decreased Cell Survival and DNA Damage in an S-Phase-Dependent Manner.Molecular cancer research : MCR · 2021Article
- (ADP-ribosyl)hydrolases: structure, function, and biology.Genes & development · 2020Review
- Nuclear PARPs and genome integrity.Genes & development · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly(ADP-ribosyl)ation (PAR) has been implicated in various aspects of the cellular response to DNA damage and genome stability. Although 17 human poly(ADP-ribose) polymerase (PARP) genes have been identified, a single poly(ADP-ribosyl) glycohydrolase (PARG) mediates PAR degradation. Here we investigated the role of PARG in the replication of human chromosomes. We show that PARG depletion affects cell proliferation and DNA synthesis, leading to replication-coupled H2AX phosphorylation. Furthermore, PARG depletion or inhibition per se slows down individual replication forks similarly to mild chemotherapeutic treatment. Electron microscopic analysis of replication intermediates reveals marked accumulation of reversed forks and single-stranded DNA (ssDNA) gaps in unperturbed PARG-defective cells. Intriguingly, while we found no physical evidence for chromosomal breakage, PARG-defective cells displayed both ataxia-telangiectasia-mutated (ATM) and ataxia-Rad3-related (ATR) activation, as well as chromatin recruitment of standard double-strand-break-repair factors, such as 53BP1 and RAD51. Overall, these data prove PAR degradation to be essential to promote resumption of replication at endogenous and exogenous lesions, preventing idle recruitment of repair factors to remodeled replication forks. Furthermore, they suggest that fork remodeling and restarting are surprisingly frequent in unperturbed cells and provide a molecular rationale to explore PARG inhibition in cancer chemotherapy.
Indexed as
Identifiers
What OpenQuestion holds
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.