ArticleGenes & development2016
Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 55 citations in OpenAlex.
- Structural insights into the MLH1-FAN1 interaction reveal an uncharacterized binding interface on MLH1.Nature communications · 2026Article
- USP7 deubiquitinase stabilizes FAN1 to support DNA crosslink repair and suppress CAG repeat expansion.Nature communications · 2026Article
- Article
- ATM promotes reversed fork processing during DNA interstrand cross-link repair.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive review on Fanconi anemia: insights into DNA interstrand cross-links, repair pathways, and associated tumors.Orphanet journal of rare diseases · 2025Review
- Breast cancer gene-1 (BRCA1) potentiates maladaptive repair after kidney injury.The Journal of experimental medicine · 2025Article
- FAN1-mediated translesion synthesis and POLQ/HELQ-mediated end joining generate interstrand crosslink-induced mutations.Nature communications · 2025Article
- Article
- A case of karyomegalic interstitial nephritis without FAN1 mutations in the setting of brentuximab, ifosfamide, and carboplatin exposure.BMC nephrology · 2024Article
- Repair of genomic interstrand crosslinks.DNA repair · 2024Review
- Modeling ofCells · 2023Article
- FAN1 removes triplet repeat extrusions via a PCNA- and RFC-dependent mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Altered Epigenetic Profiles in the Placenta of Preeclamptic and Intrauterine Growth Restriction Patients.Cells · 2023Article
- Mitochondrial ROS Triggers KIN Pathogenesis in FAN1-Deficient Kidneys.Antioxidants (Basel, Switzerland) · 2023Article
- Pathological consequences of DNA damage in the kidney.Nature reviews. Nephrology · 2023Review
- Persistent DNA damage underlies tubular cell polyploidization and progression to chronic kidney disease in kidneys deficient in the DNA repair protein FAN1.Kidney international · 2022Article
- Facile preparation of model DNA interstrand cross-link repair intermediates using ribonucleotide-containing DNA.DNA repair · 2022Article
- Recombination and restart at blocked replication forks.Current opinion in genetics & development · 2021Review
- FAN1's protection against CGG repeat expansion requires its nuclease activity and is FANCD2-independent.Nucleic acids research · 2021Article
- RecurrentKidney international reports · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Deficiency of FANCD2/FANCI-associated nuclease 1 (FAN1) in humans leads to karyomegalic interstitial nephritis (KIN), a rare hereditary kidney disease characterized by chronic renal fibrosis, tubular degeneration, and characteristic polyploid nuclei in multiple tissues. The mechanism of how FAN1 protects cells is largely unknown but is thought to involve FAN1's function in DNA interstrand cross-link (ICL) repair. Here, we describe a Fan1-deficient mouse and show that FAN1 is required for cellular and organismal resistance to ICLs. We show that the ubiquitin-binding zinc finger (UBZ) domain of FAN1, which is needed for interaction with FANCD2, is not required for the initial rapid recruitment of FAN1 to ICLs or for its role in DNA ICL resistance. Epistasis analyses reveal that FAN1 has cross-link repair activities that are independent of the Fanconi anemia proteins and that this activity is redundant with the 5'-3' exonuclease SNM1A. Karyomegaly becomes prominent in kidneys and livers of Fan1-deficient mice with age, and mice develop liver dysfunction. Treatment of Fan1-deficient mice with ICL-inducing agents results in pronounced thymic and bone marrow hypocellularity and the disappearance of c-kit(+) cells. Our results provide insight into the mechanism of FAN1 in ICL repair and demonstrate that the Fan1 mouse model effectively recapitulates the pathological features of human FAN1 deficiency.
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