ArticleNucleic acids research2023
FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Multi-omics profiling of pancreatic neuroendocrine tumors: Interplay of genomic instability and the tumor microenvironment (Review).Oncology letters · 2026Review
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- FANCD2 restrains fork progression and prevents fragility at early origins upon re-replication.Nature communications · 2026Article
- Article
- Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.Current treatment options in oncology · 2025Review
- Cytosolic DNA and intracellular CaDNA repair · 2025Review
- Synergistic protection of nascent DNA at stalled forks by MSANTD4 and BRCA1/2-RAD51.Nature chemical biology · 2025Article
- Enhanced sensitivity, robust p21 activation, and sustained DNA repair responses to interstrand crosslinks in elephant cells compared to humans.Frontiers in veterinary science · 2025Article
- Pancreatic Neuroendocrine Tumor: The Case Report of a Patient with GermlineJournal of clinical medicine · 2024Article
- Clinical relevance of double heterozygosity revealed by next-generation sequencing of homologous recombination repair pathway genes in South African breast cancer patients.Breast cancer research and treatment · 2024Article
- TCAF1 promotes TRPV2-mediated CaNature communications · 2024Article
- Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.Genes & development · 2024Article
- Molecular mechanisms of avian immunoglobulin gene diversification and prospect for industrial applications.Frontiers in immunology · 2024Review
- Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.bioRxiv : the preprint server for biology · 2023Article
- Class I HDAC Inhibition Leads to a Downregulation of FANCD2 and RAD51, and the Eradication of Glioblastoma Cells.Journal of personalized medicine · 2023Article
- RAD51 bypasses the CMG helicase to promote replication fork reversal.Science (New York, N.Y.) · 2023Article
- Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
FANCD2 protein, a key coordinator and effector of the interstrand crosslink repair pathway, is also required to prevent excessive nascent strand degradation at hydroxyurea-induced stalled forks. The RAD51 recombinase has also been implicated in regulation of resection at stalled replication forks. The mechanistic contributions of these proteins to fork protection are not well understood. Here, we used purified FANCD2 and RAD51 to study how each protein regulates DNA resection at stalled forks. We characterized three mechanisms of FANCD2-mediated fork protection: (1) The N-terminal domain of FANCD2 inhibits the essential DNA2 nuclease activity by directly binding to DNA2 accounting for over-resection in FANCD2 defective cells. (2) Independent of dimerization with FANCI, FANCD2 itself stabilizes RAD51 filaments to inhibit multiple nucleases, including DNA2, MRE11 and EXO1. (3) Unexpectedly, we uncovered a new FANCD2 function: by stabilizing RAD51 filaments, FANCD2 acts to stimulate the strand exchange activity of RAD51. Our work biochemically explains non-canonical mechanisms by which FANCD2 and RAD51 protect stalled forks. We propose a model in which the strand exchange activity of FANCD2 provides a simple molecular explanation for genetic interactions between FANCD2 and BRCA2 in the FA/BRCA fork protection pathway.
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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 Socratic graph.