ArticleCell death and differentiation2020
53BP1 loss rescues embryonic lethality but not genomic instability of BRCA1 total knockout mice.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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
34 citing papers in PubMed, 37 citations in OpenAlex.
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Assessing the Clinical Relevance ofCurrent oncology (Toronto, Ont.) · 2026Article
- 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
- Cryptic redundancy between PAR1b and PAR1a, two members of the PAR1 kinase family, in the survival of PAR1b-knockout mice.Scientific reports · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- New twist on BRCA1-mediated DNA recombination repair and tumor suppression.Trends in cell biology · 2026Review
- PALB2 and 53BP1 govern post-resection homologous recombination DNA repair.Molecular cell · 2025Article
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Shieldin and CST co-orchestrate DNA polymerase-dependent tailed-end joining reactions independently of 53BP1-governed repair pathway choice.Nature structural & molecular biology · 2025Article
- Repetitive Sequence Stability in Embryonic Stem Cells.International journal of molecular sciences · 2024Review
- Article
- Systematic investigation of BRCA1-A, -B, and -C complexes and their functions in DNA damage response and DNA repair.Oncogene · 2024Article
- BRCA1 safeguards genome integrity by activating chromosome asynapsis checkpoint to eliminate recombination-defective oocytes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The chromatin-associated 53BP1 ortholog, HSR-9, regulates recombinational repair andbioRxiv : the preprint server for biology · 2024Article
- STIM1 translocation to the nucleus protects cells from DNA damage.Nucleic acids research · 2024Article
- PTEN-mediated dephosphorylation of 53BP1 confers cellular resistance to DNA damage in cancer cells.Molecular oncology · 2024Article
- MBD1 protects replication fork stability by recruiting PARP1 and controlling transcription-replication conflicts.Cancer gene therapy · 2024Article
- Brca1 Mouse Models: Functional Insights and Therapeutic Opportunities.Journal of molecular biology · 2024Review
- How to sensitize glioblastomas to temozolomide chemotherapy: a gap-centered view.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRCA1 is critical for DNA double-strand break (DSB) repair by homologous recombination (HR). BRCA1 deficient mice are embryonic lethal. Previous studies have shown that 53BP1 knockout (KO) rescues embryonic lethality of BRCA1 hypomorphic mutant mice by restoring HR. Here, we show that 53BP1 KO can partially rescue embryonic lethality of BRCA1 total KO mice, but HR is not restored in BRCA1-53BP1 double knockout (DKO) mice. As a result, BRCA1-53BP1 DKO cells are extremely sensitive to PARP inhibitors (PARPi). In addition to HR deficiency, BRCA1-53BP1 DKO cells have elevated microhomology-mediated end joining (MMEJ) activity and G2/M cell cycle checkpoint defects, causing severe genomic instability in these cells. Interestingly, BRCA1-53BP1 DKO mice rapidly develop thymic lymphoma that is 100% penetrant, which is not observed in any BRCA1 mutant mice rescued by 53BP1 KO. Taken together, our study reveals that 53BP1 KO can partially rescue embryonic lethality caused by complete BRCA1 loss without rescuing HR-related defects. This finding suggests that loss of 53BP1 can support the development of cancers with silenced BRCA1 expression without causing PARPi resistance.
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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.