ArticleBlood2021
SLFN11 promotes stalled fork degradation that underlies the phenotype in Fanconi anemia cells.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 33 citations in OpenAlex.
- Replication Stress Tolerance in Adult T-Cell Leukemia.Biomolecules · 2026Review
- Alkylating agents activate an SLFN11-dependent vulnerability that confers PARP-1 inhibitor sensitivity in kidney cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- SLFN5 restrains type I interferon responses and promotes glioblastoma via its N-terminal Schlafen core domain.Communications biology · 2026Article
- Ubiquitin-dependent recruitment of SLFN11 to chromatin is regulated by deubiquitinase (DUB) and RNF168.Research square · 2026Article
- Development of Stearic Acid Nanoemulsion for Therapeutic Delivery of Talazoparib Against Breast Cancer.Pharmaceutics · 2026Article
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance axis to restrain gapped DNA synthesis in response to replication stress.Nature communications · 2025Article
- Recurrent Evolutionary Innovations in Rodent and Primate Schlafen Genes.Genome biology and evolution · 2025Article
- DNA cross-link repair deficiency enhances human cell sensitivity to colibactin-induced genotoxicity.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Article
- SLFN11, far from being limited to responding to cancer DNA damage.Clinical and experimental medicine · 2025Review
- SLFN11 Restricts LINE-1 Mobility.Cells · 2025Article
- Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia.The Journal of experimental medicine · 2025Article
- Targeting SLFN11-regulated pathways restores chemotherapy sensitivity in AML.Blood neoplasia · 2024Article
- p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.Nucleic acids research · 2024Article
- ATR/Chk1 interacting lncRNA modulates DNA damage response to induce breast cancer chemoresistance.Cell insight · 2024Article
- The Compromised Fanconi Anemia Pathway in Prelamin A-Expressing Cells Contributes to Replication Stress-Induced Genomic Instability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor.World journal of gastrointestinal oncology · 2024Article
- The crucial role of single-stranded DNA binding in enhancing sensitivity to DNA-damaging agents for Schlafen 11 and Schlafen 13.iScience · 2023Article
- Mitotic DNA Synthesis in Untransformed Human Cells Preserves Common Fragile Site Stability via a FANCD2-Driven Mechanism That Requires HELQ.Journal of molecular biology · 2023Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Fanconi anemia (FA) is a hereditary disorder caused by mutations in any 1 of 22 FA genes. The disease is characterized by hypersensitivity to interstrand crosslink (ICL) inducers such as mitomycin C (MMC). In addition to promoting ICL repair, FA proteins such as RAD51, BRCA2, or FANCD2 protect stalled replication forks from nucleolytic degradation during replication stress, which may have a profound impact on FA pathophysiology. Recent studies showed that expression of the putative DNA/RNA helicase SLFN11 in cancer cells correlates with cell death on chemotherapeutic treatment. However, the underlying mechanisms of SLFN11-mediated DNA damage sensitivity remain unclear. Because SLFN11 expression is high in hematopoietic stem cells, we hypothesized that SLFN11 depletion might ameliorate the phenotypes of FA cells. Here we report that SLFN11 knockdown in the FA patient-derived FANCD2-deficient PD20 cell line improved cell survival on treatment with ICL inducers. FANCD2-/-SLFN11-/- HAP1 cells also displayed phenotypic rescue, including reduced levels of MMC-induced chromosome breakage compared with FANCD2-/- cells. Importantly, we found that SLFN11 promotes extensive fork degradation in FANCD2-/- cells. The degradation process is mediated by the nucleases MRE11 or DNA2 and depends on the SLFN11 ATPase activity. This observation was accompanied by an increased RAD51 binding at stalled forks, consistent with the role of RAD51 antagonizing nuclease recruitment and subsequent fork degradation. Suppression of SLFN11 protects nascent DNA tracts even in wild-type cells. We conclude that SLFN11 destabilizes stalled replication forks, and this function may contribute to the attrition of hematopoietic stem cells in FA.
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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.