ArticleNature2015
REV7 counteracts DNA double-strand break resection and affects PARP inhibition.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 384 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
384 citing papers in PubMed, 1 synthesis or guideline pooled it, 589 citations in OpenAlex.
- Knowledge mapping of global trends in DNA damage repair-related breast cancer research: a bibliometric study.Frontiers in oncology · 2025Pooled it
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- Youthfulness of marrow AdipoqBone research · 2026Article
- SNORA23-KDM5C epigenetic axis mediates dual DNA repair pathways to drive radioresistance in esophageal squamous cell carcinoma.Cell death and differentiation · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- 53BP1-independent Shieldin-BRCA1 antagonism at replication-coupled double-strand breaks.Nature communications · 2026Article
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- Telmisartan increases olaparib efficacy in homologous recombination proficient tumors by augmenting type I interferon production.Journal for immunotherapy of cancer · 2026Article
- Polθ activity modulates sensitivity to standard therapies in DNMT3A-deficient leukemia.Cell reports. Medicine · 2026Article
- The mitochondrial translocation of phosphorylated EZH2 promotes PARP inhibitor resistance in BRCA1-deficient epithelial ovarian cancer.Cell discovery · 2026Article
- Chromatin-intrinsic mechanisms determine orientation-specific class switch recombination.Nature communications · 2026Article
- Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.Nature cell biology · 2026Article
- MDC1 counteracts replication fork reversal and mediates chemosensitivity in BRCA1/2-deficient tumors.Oncogene · 2026Article
- KIF2A-mediated microtubule-dependent nuclear envelope invagination drives nonhomologous end joining.Nucleic acids research · 2026Article
- Targeting MAD2L2-dependent translesion synthesis impairs DNA damage tolerance and enhances cellular response to cisplatin.Frontiers in cell and developmental biology · 2026Article
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- Unraveling the Resistance: Challenges and Advances in PARP Inhibitor Therapy for BRCA1/2 Breast Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
324 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 9 institutions in 6 countries.
Funding
Abstract
Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway. In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with breast or ovarian cancers. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of drug resistance, but this does not explain resistance in all cases. In particular, little is known about BRCA1-independent restoration of HR. Here we show that loss of REV7 (also known as MAD2L2) in mouse and human cell lines re-establishes CTIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, which is reversed by ATM kinase inhibition. REV7 is recruited to DSBs in a manner dependent on the H2AX-MDC1-RNF8-RNF168-53BP1 chromatin pathway, and seems to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance. Finally, we establish that REV7 blocks DSB resection to promote non-homologous end-joining during immunoglobulin class switch recombination. Our results reveal an unexpected crucial function of REV7 downstream of 53BP1 in coordinating pathological DSB repair pathway choices in BRCA1-deficient cells.
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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.