ArticleNature cell biology2018
Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells.
Article in Nature cell biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 278 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
278 citing papers in PubMed, 412 citations in OpenAlex.
- Resistance to neoadjuvant talazoparib in triple-negative breast cancer by BRN2-induced ATR/STAT3 pathways or SHLD2 subclone expansion.Proceedings of the National Academy of Sciences of the United States of America · 2026Trial
- The Pharmacologic Profile of ART6043, a First-in-Class Clinical DNA Polymerase Theta Polymerase Domain Inhibitor Potentiating PARP Inhibitor Efficacy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Distinct functions of mammalian RAD51 paralogs in genome maintenance.Biochemical Society transactions · 2026Review
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- Dynamic chromatin tethering of MDC1 regulates genome stability.Nucleic acids research · 2026Article
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Docking-Based Virtual Screening Identifies a Small-Molecule Inhibitor of the Translesion Synthesis REV7/REV3 Protein-Protein Interaction.ChemMedChem · 2026Article
- RAD51 in Breast Cancer: From Vulnerability to Resistance.World journal of oncology · 2026Review
- Merlin deficiency supports an immunosuppressive milieu in breast cancer.Cell death discovery · 2026Article
- 53BP1-independent Shieldin-BRCA1 antagonism at replication-coupled double-strand breaks.Nature communications · 2026Article
- Article
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Finding novel vulnerabilities of hypomorphic BRCA1 alleles.Molecular oncology · 2026Article
- 53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination.Science advances · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- A mutational scar-based genome-wide map of DNA double-strand break repair.Nature communications · 2026Article
- Tripleknock: predicting lethal effect of three-gene knockout in bacteria by deep learning.Scientific reports · 2026Article
- Genome-wide CRISPR-Cas9 screening identifies CLK1 inhibition as a strategy to restore PARP inhibitor sensitivity via ERCC1 isoform switching.Protein & cell · 2026Article
- Chromatin-intrinsic mechanisms determine orientation-specific class switch recombination.Nature communications · 2026Article
- MDC1 counteracts replication fork reversal and mediates chemosensitivity in BRCA1/2-deficient tumors.Oncogene · 2026Article
218 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
30 authors at 8 institutions in 6 countries.
Funding
Abstract
BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we conducted whole-genome CRISPR-Cas9 synthetic-viability/resistance screens in BRCA1-deficient breast cancer cells treated with PARP inhibitors. We identified two previously uncharacterized proteins, C20orf196 and FAM35A, whose inactivation confers strong PARP-inhibitor resistance. Mechanistically, we show that C20orf196 and FAM35A form a complex, 'Shieldin' (SHLD1/2), with FAM35A interacting with single-stranded DNA through its C-terminal oligonucleotide/oligosaccharide-binding fold region. We establish that Shieldin acts as the downstream effector of 53BP1/RIF1/MAD2L2 to promote DNA double-strand break (DSB) end-joining by restricting DSB resection and to counteract homologous recombination by antagonizing BRCA2/RAD51 loading in BRCA1-deficient cells. Notably, Shieldin inactivation further sensitizes BRCA1-deficient cells to cisplatin, suggesting how defining the SHLD1/2 status of BRCA1-deficient tumours might aid patient stratification and yield new treatment opportunities. Highlighting this potential, we document reduced SHLD1/2 expression in human breast cancers displaying intrinsic or acquired PARP-inhibitor resistance.
Indexed as
Identifiers
What OpenQuestion holds
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.