ArticleThe Journal of biological chemistry2015
FANCD2-associated nuclease 1, but not exonuclease 1 or flap endonuclease 1, is able to unhook DNA interstrand cross-links in vitro.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The trial behind it
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Who cites it
35 citing papers in PubMed.
- Mechanisms of Hydroxyurea-Mediated DNA Damage Potentiation in Fanconi Anemia Cells.International journal of molecular sciences · 2026Article
- USP7 deubiquitinase stabilizes FAN1 to support DNA crosslink repair and suppress CAG repeat expansion.Nature communications · 2026Article
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- FAN1-mediated translesion synthesis and POLQ/HELQ-mediated end joining generate interstrand crosslink-induced mutations.Nature communications · 2025Article
- Repair of genomic interstrand crosslinks.DNA repair · 2024Review
- Replication-Independent ICL Repair: From Chemotherapy to Cell Homeostasis.Journal of molecular biology · 2024Review
- Purification, full-length sequencing and genomic origin mapping of eccDNA.Nature protocols · 2023Review
- FANCD2-Associated Nuclease 1 Partially Compensates for the Lack of Exonuclease 1 in Mismatch Repair.Molecular and cellular biology · 2021Article
- Coordinated Cut and Bypass: Replication of Interstrand Crosslink-Containing DNA.Frontiers in cell and developmental biology · 2021Review
- FAN1, a DNA Repair Nuclease, as a Modifier of Repeat Expansion Disorders.Journal of Huntington's disease · 2021Review
- The SNM1A DNA repair nuclease.DNA repair · 2020Review
- XPF-ERCC1: Linchpin of DNA crosslink repair.PLoS genetics · 2020Article
- Genetic Mapping of Climbing and Mimicry: Two Behavioral Traits Degraded During Silkworm Domestication.Frontiers in genetics · 2020Article
- Fanconi Anemia Pathway: Mechanisms of Breast Cancer Predisposition Development and Potential Therapeutic Targets.Frontiers in cell and developmental biology · 2020Review
- CRL4 ubiquitin ligase stimulates Fanconi anemia pathway-induced single-stranded DNA-RPA signaling.BMC cancer · 2019Article
- Structure-specific endonuclease activity of SNM1A enables processing of a DNA interstrand crosslink.Nucleic acids research · 2018Article
- Ubiquitylation at the Fork: Making and Breaking Chains to Complete DNA Replication.International journal of molecular sciences · 2018Review
- A senataxin-associated exonuclease SAN1 is required for resistance to DNA interstrand cross-links.Nature communications · 2018Article
- Structural mechanism of DNA interstrand cross-link unhooking by the bacterial FAN1 nuclease.The Journal of biological chemistry · 2018Article
- Multifaceted Fanconi Anemia Signaling.Trends in genetics : TIG · 2018Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Cisplatin and its derivatives, nitrogen mustards and mitomycin C, are used widely in cancer chemotherapy. Their efficacy is linked primarily to their ability to generate DNA interstrand cross-links (ICLs), which effectively block the progression of transcription and replication machineries. Release of this block, referred to as unhooking, has been postulated to require endonucleases that incise one strand of the duplex on either side of the ICL. Here we investigated how the 5' flap nucleases FANCD2-associated nuclease 1 (FAN1), exonuclease 1 (EXO1), and flap endonuclease 1 (FEN1) process a substrate reminiscent of a replication fork arrested at an ICL. We now show that EXO1 and FEN1 cleaved the substrate at the boundary between the single-stranded 5' flap and the duplex, whereas FAN1 incised it three to four nucleotides in the double-stranded region. This affected the outcome of processing of a substrate containing a nitrogen mustard-like ICL two nucleotides in the duplex region because FAN1, unlike EXO1 and FEN1, incised the substrate predominantly beyond the ICL and, therefore, failed to release the 5' flap. We also show that FAN1 was able to degrade a linear ICL substrate. This ability of FAN1 to traverse ICLs in DNA could help to elucidate its biological function, which is currently unknown.
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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 OpenQuestion graph.