ArticleThe Journal of biological chemistry2015
A quantitative assay reveals ligand specificity of the DNA scaffold repair protein XRCC1 and efficient disassembly of complexes of XRCC1 and the poly(ADP-ribose) polymerase 1 by poly(ADP-ribose) glycohydrolase.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis.NAR cancer · 2025Article
- PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation.EMBO reports · 2024Article
- Poly-ADP-ribosylation dynamics, signaling, and analysis.Environmental and molecular mutagenesis · 2024Review
- Divalent and multivalent cations control liquid-like assembly of poly(ADP-ribosyl)ated PARP1 into multimolecular associates in vitro.Communications biology · 2024Article
- Deltex family E3 ligases specifically ubiquitinate the terminal ADP-ribose of poly(ADP-ribosyl)ation.Biochemical and biophysical research communications · 2024Article
- PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation.bioRxiv : the preprint server for biology · 2024Article
- Article
- PARP1 and XRCC1 exhibit a reciprocal relationship in genotoxic stress response.Cell biology and toxicology · 2023Article
- Article
- FUS Microphase Separation: Regulation by Nucleic Acid Polymers and DNA Repair Proteins.International journal of molecular sciences · 2022Article
- PARP inhibitors trap PARP2 and alter the mode of recruitment of PARP2 at DNA damage sites.Nucleic acids research · 2022Article
- Research Progress on Mono-ADP-Ribosyltransferases in Human Cell Biology.Frontiers in cell and developmental biology · 2022Review
- X-ray repair cross-complementing protein 1 (XRCC1) loss promotes β-lapachone -induced apoptosis in pancreatic cancer cells.BMC cancer · 2021Article
- Why structure and chain length matter: on the biological significance underlying the structural heterogeneity of poly(ADP-ribose).Nucleic acids research · 2021Article
- Functional Roles of PARP2 in Assembling Protein-Protein Complexes Involved in Base Excision DNA Repair.International journal of molecular sciences · 2021Article
- An atypical BRCT-BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIα within a flexible DNA repair complex.Nucleic acids research · 2021Article
- Selective monitoring of the protein-free ADP-ribose released by ADP-ribosylation reversal enzymes.PloS one · 2021Article
- Article
- Clinical PARP inhibitors do not abrogate PARP1 exchange at DNA damage sites in vivo.Nucleic acids research · 2020Article
- Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair.Nature communications · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The posttranslational modification of proteins with poly(ADP-ribose) (PAR) regulates protein-protein interactions in DNA repair, gene expression, chromatin structure, and cell fate determination. The PAR polymerase PARP1 binds to damaged chromatin and synthesizes PAR chains to signal DNA damage and recruit the DNA repair scaffold, XRCC1. Pharmacological blockade of PARP1 enzymatic activity impairs XRCC1-dependent repair of DNA damage and selectively kills cancer cells lacking other DNA repair functions. As such, PARP inhibitors are promising new therapies for repair-deficient tumors such as BRCA mutated breast cancers. Although the XRCC1-PARP1 complex is relevant to the proposed therapeutic mechanism of PARP inhibitors, the physical makeup and dynamics of this complex are not well characterized at the molecular level. Here we describe a fluorescence-based, real-time assay that quantitatively monitors interactions between PARylated PARP1 and XRCC1. Using this assay, we show that the PAR posttranslational modification by itself is a high affinity ligand for XRCC1, requiring a minimum chain length of 7 ADP-ribose units in the oligo(ADP-ribose) ligand for a stable interaction with XRCC1. This discrete binding interface enables the PAR glycohydrolase (PARG) to completely disassemble the PARP1-XRCC1 complex without assistance from a mono(ADP-ribose) glycohydrolase. Our quantitative, real-time assay of PAR-dependent protein-protein interactions and PAR turnover by PARG is an excellent tool for high-throughput screening to identify pharmacological modulators of PAR metabolism that may be useful therapeutic alternatives to PARP inhibitors.
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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.