ArticleProceedings of the National Academy of Sciences of the United States of America2011
Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
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131 citing papers in PubMed, 197 citations in OpenAlex.
- Real-time visualization of spatial and temporal coordination in resolvase-mediated Holliday junction binding.iScience · 2026Article
- Lesions initiating spontaneous mitotic crossover are minimally subject to non-homologous end joining.bioRxiv : the preprint server for biology · 2026Article
- Micronuclei: origins, assays, mechanisms, diseases and treatments.Signal transduction and targeted therapy · 2026Review
- Proteome-widebioRxiv : the preprint server for biology · 2025Article
- MCM8/9 and FANCD2 interact within a shared pathway in response to replication stress caused by DNA crosslinks.DNA repair · 2025Article
- RNF4 and USP7 coordinate spatial regulation of SLX4 stability within the PML nuclear bodies.Nucleic acids research · 2025Article
- Head and Neck Cancer in Fanconi Anemia: Clinical Challenges and Molecular Insights into a DNA Repair Disorder.Cancers · 2025Review
- RAD18- and BRCA1-dependent pathways promote cellular tolerance to the nucleoside analog ganciclovir.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Deciphering the role of post-translational modifications in fanconi anemia proteins and their influence on tumorigenesis.Cancer gene therapy · 2024Review
- Dual role of proliferating cell nuclear antigen monoubiquitination in facilitating Fanconi anemia-mediated interstrand crosslink repair.PNAS nexus · 2024Article
- REV3 promotes cellular tolerance to 5-fluorodeoxyuridine by activating translesion DNA synthesis and intra-S checkpoint.PLoS genetics · 2024Article
- FANCD2 counteracts OMolecular biology reports · 2024Article
- Human AAA+ ATPase FIGNL1 suppresses RAD51-mediated ultra-fine bridge formation.Nucleic acids research · 2024Article
- A minimal Fanconi Anemia complex in early diverging fungi.Scientific reports · 2024Article
- The proofreading exonuclease of leading-strand DNA polymerase epsilon prevents replication fork collapse at broken template strands.Nucleic acids research · 2023Article
- Review
- Implications of ubiquitination and the maintenance of replication fork stability in cancer therapy.Bioscience reports · 2023Review
- The structure-specific endonuclease complex SLX4-XPF regulates Tus-Ter-induced homologous recombination.Nature structural & molecular biology · 2022Article
- Conserved function of Drosophila Fancd2 monoubiquitination in response to double-strand DNA breaks.G3 (Bethesda, Md.) · 2022Article
- Review
71 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interstrand cross-links (ICLs) block replication and transcription and thus are highly cytotoxic. In higher eukaryotes, ICLs processing involves the Fanconi anemia (FA) pathway and homologous recombination. Stalled replication forks activate the eight-subunit FA core complex, which ubiquitylates FANCD2-FANCI. Once it is posttranslationally modified, this heterodimer recruits downstream members of the ICL repairosome, including the FAN1 nuclease. However, ICL processing has been shown to also involve MUS81-EME1 and XPF-ERCC1, nucleases known to interact with SLX4, a docking protein that also can bind another nuclease, SLX1. To investigate the role of SLX4 more closely, we disrupted the SLX4 gene in avian DT40 cells. SLX4 deficiency caused cell death associated with extensive chromosomal aberrations, including a significant fraction of isochromatid-type breaks, with sister chromatids broken at the same site. SLX4 thus appears to play an essential role in cell proliferation, probably by promoting the resolution of interchromatid homologous recombination intermediates. Because ubiquitylation plays a key role in the FA pathway, and because the N-terminal region of SLX4 contains a ubiquitin-binding zinc finger (UBZ) domain, we asked whether this domain is required for ICL processing. We found that SLX4(-/-) cells expressing UBZ-deficient SLX4 were selectively sensitive to ICL-inducing agents, and that the UBZ domain was required for interaction of SLX4 with ubiquitylated FANCD2 and for its recruitment to DNA-damage foci generated by ICL-inducing agents. Our findings thus suggest that ubiquitylated FANCD2 recruits SLX4 to DNA damage sites, where it mediates the resolution of recombination intermediates generated during the processing of ICLs.
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