ArticleDNA repair2019
Impeding the single-strand annealing pathway of DNA double-strand break repair by withaferin A-mediated FANCA degradation.
Article in DNA repair, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- FANCA-dependent FEN1 recruitment suppresses transcription-replication conflicts and PARPi sensitivity.Molecular cell · 2026Article
- Article
- Oncogenic properties of wild-type DNA repair gene FANCA in breast cancer.Cell reports · 2025Article
- Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Article
- Single-Strand Annealing in Cancer.International journal of molecular sciences · 2021Review
- Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives.Biomedicines · 2020Review
- Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera.Environmental science and pollution research international · 2020Review
- Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine.The EPMA journal · 2020Review
- Fanconi anemia pathway as a prospective target for cancer intervention.Cell & bioscience · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
FANCA is a key player in the canonical Fanconi anemia (FA) repair pathway. We have recently shown that FANCA also plays an important role in the single-strand annealing sub-pathway (SSA) of DNA double-strand break (DSB) repair by biochemically catalyzing single-strand annealing. Here, we report that a steroidal lactone withaferin A (WA) specifically impedes SSA repair by promoting FANCA downregulation at a sub-micromolar concentration range. We find that WA causes FANCA downregulation post-translationally in a proteasome-dependent manner. This WA-mediated downregulation is achieved through HSP90 inhibition and disruption of the FANCA-HSP90 interaction. WA-mediated FANCA degradation significantly reduces cellular SSA repair, abolishes FANCD2 monoubiquitination, elevates sensitivity to mitomycin C, and results in accumulation of DSBs. Importantly, the WA-induced defect in SSA repair is highly dependent on the absence of FANCA protein and overexpression of exogenous WT-FANCA protein in WA-treated cells significantly complements the repair defect.
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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.