ArticleMolecular cell2021
Loss of nuclear DNA ligase III reverts PARP inhibitor resistance in BRCA1/53BP1 double-deficient cells by exposing ssDNA gaps.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 88 citations in OpenAlex.
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Article
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- CHD1L maintains genome integrity by facilitating okazaki fragment maturation.Nucleic acids research · 2026Article
- Mechanisms of PARP Inhibitor Resistance: From Replication Gap Biology and Transcription-Replication Conflicts to PROTAC-Based Next-Generation Strategies.Environmental and molecular mutagenesis · 2026Review
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Review
- Cancer metabolism in radiation sensitization - complementary roles of O-GlcNAc transferase and PARP1.Journal of cell science · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Characterizing a murine breast cancer mouse model reveals chromosomal abnormalities in structure and number of single-cell clones and the presence of rare cancer stem cell-like phenotypes.Animal models and experimental medicine · 2026Article
- The expanding roles of homologous recombination proteins in genome stability.The EMBO journal · 2026Review
- Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis.NAR cancer · 2025Article
- Mechanistic insights into the monotherapy and combination potential of FEN1 inhibition in cancer therapy.Nucleic acids research · 2025Article
- EXO1 as a therapeutic target for Fanconi Anaemia, ZRSR2 and BRCA1-A complex deficient cancers.Nature communications · 2025Article
- RAD51 is chromatin enriched and targetable in BRCA1-deficient cells.Molecular cell · 2025Article
- Article
- Detecting likely germline variants during tumor-based molecular profiling.The Journal of clinical investigation · 2025Review
- Mechanisms and regulation of DNA end resection in the maintenance of genome stability.Nature reviews. Molecular cell biology · 2025Review
- The DNA-PKcs/JNK/p53 pathway underlies changes in cell fate decision toward death during DNA replication catastrophe.Nucleic acids research · 2025Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 8 institutions in 7 countries.
Funding
Abstract
Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, preclinical and clinical research with PARPi has revealed multiple resistance mechanisms, highlighting the need for identification of novel functional biomarkers and combination treatment strategies. Functional genetic screens performed in cells and organoids that acquired resistance to PARPi by loss of 53BP1 identified loss of LIG3 as an enhancer of PARPi toxicity in BRCA1-deficient cells. Enhancement of PARPi toxicity by LIG3 depletion is dependent on BRCA1 deficiency but independent of the loss of 53BP1 pathway. Mechanistically, we show that LIG3 loss promotes formation of MRE11-mediated post-replicative ssDNA gaps in BRCA1-deficient and BRCA1/53BP1 double-deficient cells exposed to PARPi, leading to an accumulation of chromosomal abnormalities. LIG3 depletion also enhances efficacy of PARPi against BRCA1-deficient mammary tumors in mice, suggesting LIG3 as a potential therapeutic target.
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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.