ArticleNature cancer2021
The CIP2A-TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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85 citing papers in PubMed, 112 citations in OpenAlex.
- The BRCA1 coiled-coil domain is dispensable for suppression of tandem duplications and tolerance of FANCM loss.The EMBO journal · 2026Article
- DNA end-resection is stimulated by an interaction between BRCA1 exon 11 and TOPBP1.EMBO reports · 2026Article
- Targeting Polθ Helicase with RP-3467: Preclinical Validation and Clinical Response in a gmedRxiv : the preprint server for health sciences · 2026Article
- Dynamic chromatin tethering of MDC1 regulates genome stability.Nucleic acids research · 2026Article
- Disruption of microhomology-mediated end joining in Ewing sarcoma.Molecular cell · 2026Article
- Development of a structurally distinct TopBP1 inhibitor that enhances PARP blockade and reverses osimertinib resistance.Science advances · 2026Article
- CIP2A recruits SLX4-MUS81-XPF in mitosis and protects against replication stress.EMBO reports · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Spatiotemporal organisation of residual disease in mouse and human BRCA1-deficient mammary tumours and breast cancer.Nature communications · 2026Article
- Finding novel vulnerabilities of hypomorphic BRCA1 alleles.Molecular oncology · 2026Article
- A mutational scar-based genome-wide map of DNA double-strand break repair.Nature communications · 2026Article
- TOPBP1-PLK1 interaction preserves genome integrity during mitosis.Nucleic acids research · 2026Article
- Review
- Biomimetic PD-1 macrophage nanoplatform for Cip2a silencing and immune activation in oral squamous cell carcinoma.Journal of nanobiotechnology · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Uncovering genetic interactions in the DNA repair network in response to endogenous damage and ionizing radiation.Cell reports · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- CIP2A mediates mitotic recruitment of SLX4/MUS81/XPF to resolve replication stress-induced DNA lesions.Nature communications · 2025Article
- The CIP2A-TOPBP1 axis facilitates mitotic DNA repair via MiDAS and MMEJ.Nature communications · 2025Article
- Megabase-scale loss of heterozygosity provoked by CRISPR-Cas9 DNA double-strand breaks.Molecular cell · 2025Article
25 more citing papers are in PubMed but not listed here.
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25 authors at 4 institutions in 3 countries.
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Abstract
BRCA1/2-mutated cancer cells adapt to the genome instability caused by their deficiency in homologous recombination (HR). Identification of these adaptive mechanisms may provide therapeutic strategies to target tumors caused by the loss of these genes. In the present study, we report genome-scale CRISPR-Cas9 synthetic lethality screens in isogenic pairs of BRCA1- and BRCA2-deficient cells and identify CIP2A as an essential gene in BRCA1- and BRCA2-mutated cells. CIP2A is cytoplasmic in interphase but, in mitosis, accumulates at DNA lesions as part of a complex with TOPBP1, a multifunctional genome stability factor. Unlike PARP inhibition, CIP2A deficiency does not cause accumulation of replication-associated DNA lesions that require HR for their repair. In BRCA-deficient cells, the CIP2A-TOPBP1 complex prevents lethal mis-segregation of acentric chromosomes that arises from impaired DNA synthesis. Finally, physical disruption of the CIP2A-TOPBP1 complex is highly deleterious in BRCA-deficient tumors, indicating that CIP2A represents an attractive synthetic lethal therapeutic target for BRCA1- and BRCA2-mutated cancers.
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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.