ArticleCommunications biology2022
FANCD2 promotes mitotic rescue from transcription-mediated replication stress in SETX-deficient cancer cells.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Polymerase face-off: emerging concepts in transcription-replication coordination.EMBO reports · 2026Review
- The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts.Nucleic acids research · 2026Article
- Identification of DNA Replication Stress-Related Genes as Prognostic Biomarkers for Bladder Cancer.Combinatorial chemistry & high throughput screening · 2026Article
- Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.Cancer research · 2025Article
- Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells.Cell reports · 2025Article
- TopBP1 coordinates DNA repair synthesis in mitosis via recruitment of the nuclease scaffold SLX4.Communications biology · 2025Article
- PLK1 Inhibition Induces Synthetic Lethality in Fanconi Anemia Pathway-Deficient Acute Myeloid Leukemia.Cancer research communications · 2025Article
- Transcription-replication conflicts drive R-loop-dependent nucleosome eviction and require DOT1L activity for transcription recovery.Nucleic acids research · 2025Article
- DNMT1 prolonged absence is a tunable cellular stress that triggers cell proliferation arrest to protect from major DNA methylation loss.Cellular and molecular life sciences : CMLS · 2024Article
- Understanding DNA replication and replication stress as avenues to combat cancer.Communications biology · 2024Article
- Senataxin RNA/DNA helicase promotes replication restart at co-transcriptional R-loops to prevent MUS81-dependent fork degradation.Nucleic acids research · 2024Article
- RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity.Genes & development · 2024Review
- Replication stress as a driver of cellular senescence and aging.Communications biology · 2024Review
- Transcription-Replication Conflicts as a Source of Genome Instability.Annual review of genetics · 2023Review
- Mitotic DNA Synthesis in Untransformed Human Cells Preserves Common Fragile Site Stability via a FANCD2-Driven Mechanism That Requires HELQ.Journal of molecular biology · 2023Article
- The Role of γH2AX in Replication Stress-induced Carcinogenesis: Possible Links and Recent Developments.Cancer diagnosis & prognosisReview
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication stress (RS) is a leading cause of genome instability and cancer development. A substantial source of endogenous RS originates from the encounter between the transcription and replication machineries operating on the same DNA template. This occurs predominantly under specific contexts, such as oncogene activation, metabolic stress, or a deficiency in proteins that specifically act to prevent or resolve those transcription-replication conflicts (TRCs). One such protein is Senataxin (SETX), an RNA:DNA helicase involved in resolution of TRCs and R-loops. Here we identify a synthetic lethal interaction between SETX and proteins of the Fanconi anemia (FA) pathway. Depletion of SETX induces spontaneous under-replication and chromosome fragility due to active transcription and R-loops that persist in mitosis. These fragile loci are targeted by the Fanconi anemia protein, FANCD2, to facilitate the resolution of under-replicated DNA, thus preventing chromosome mis-segregation and allowing cells to proliferate. Mechanistically, we show that FANCD2 promotes mitotic DNA synthesis that is dependent on XPF and MUS81 endonucleases. Importantly, co-depleting FANCD2 together with SETX impairs cancer cell proliferation, without significantly affecting non-cancerous cells. Therefore, we uncovered a synthetic lethality between SETX and FA proteins for tolerance of transcription-mediated RS that may be exploited for cancer therapy.
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