ArticleNucleic acids research2021
Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Clinical Effect of Fuzheng Guben Decoction in the Treatment of Localized Prostate Cancer and Its Influence on Immune Function under Continuous Nursing Intervention.Contrast media & molecular imaging · 2022Trial
- Recurrent DNA break clusters drive replication-stress-induced copy number variants and genome diversification.Nature communications · 2026Article
- Transcription at an inducible common fragile site reveals replication origin strength hierarchy.Nucleic acids research · 2026Article
- Replication stress induces POLQ-mediated structural variant formation throughout common fragile sites after entry into mitosis.Nature communications · 2024Article
- FANCD2 genome binding is nonrandom and is enriched at large transcriptionally active neural genes prone to copy number variation.Functional & integrative genomics · 2024Article
- Linear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters.Nature communications · 2024Article
- Integrated analysis ofCell cycle (Georgetown, Tex.) · 2024Review
- Insights into common fragile site instability: DNA replication challenges at DNA repeat sequences.Emerging topics in life sciences · 2023Article
- Replication stress causes delayed mitotic entry and chromosome 12 fragility at the ANKS1B large neuronal gene in human induced pluripotent stem cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Article
- Acetylcholine promotes chronic stress-induced lung adenocarcinoma progression via α5-nAChR/FHIT pathway.Cellular and molecular life sciences : CMLS · 2023Article
- Mistimed origin licensing and activation stabilize common fragile sites under tight DNA-replication checkpoint activation.Nature structural & molecular biology · 2023Article
- Review
- FANCD2 promotes mitotic rescue from transcription-mediated replication stress in SETX-deficient cancer cells.Communications biology · 2022Article
- Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells.Scientific reports · 2022Article
- Common Threads: Aphidicolin-Inducible and Folate-Sensitive Fragile Sites in the Human Genome.Frontiers in genetics · 2021Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
Impaired replication progression leads to de novo copy number variant (CNV) formation at common fragile sites (CFSs). We previously showed that these hotspots for genome instability reside in late-replicating domains associated with large transcribed genes and provided indirect evidence that transcription is a factor in their instability. Here, we compared aphidicolin (APH)-induced CNV and CFS frequency between wild-type and isogenic cells in which FHIT gene transcription was ablated by promoter deletion. Two promoter-deletion cell lines showed reduced or absent CNV formation and CFS expression at FHIT despite continued instability at the NLGN1 control locus. APH treatment led to critical replication delays that remained unresolved in G2/M in the body of many, but not all, large transcribed genes, an effect that was reversed at FHIT by the promoter deletion. Altering RNase H1 expression did not change CNV induction frequency and DRIP-seq showed a paucity of R-loop formation in the central regions of large genes, suggesting that R-loops are not the primary mediator of the transcription effect. These results demonstrate that large gene transcription is a determining factor in replication stress-induced genomic instability and support models that CNV hotspots mainly result from the transcription-dependent passage of unreplicated DNA into mitosis.
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