ArticleCurrent biology : CB2014
Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity.
Article in Current biology : CB, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Insights into Spt6: a histone chaperone that functions in transcription, DNA replication, and genome stability.Trends in genetics : TIG · 2023Review
- Coupling DNA Replication and Spindle Function inCells · 2021Review
- High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts.Genome biology · 2021Article
- The role of FACT in managing chromatin: disruption, assembly, or repair?Nucleic acids research · 2020Review
- Inhibition of spindle extension through the yeast S phase checkpoint is coupled to replication fork stability and the integrity of centromeric DNA.Molecular biology of the cell · 2019Article
- Article
- A conserved genetic interaction between Spt6 and Set2 regulates H3K36 methylation.Nucleic acids research · 2019Article
- Comprehensive profiling of the fission yeast transcription start site activity during stress and media response.Nucleic acids research · 2019Article
- Spt6 Is Required for the Fidelity of Promoter Selection.Molecular cell · 2018Article
- Spurious transcription and its impact on cell function.Transcription · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Intragenic transcripts initiate within the coding region of a gene, thereby producing shorter mRNAs and proteins. Although intragenic transcripts are widely expressed [1], their role in the functional regulation of genes remains largely unknown. In budding yeast, DNA replication stress activates the S phase checkpoint that stabilizes replication forks and arrests cells in S phase with a short spindle [2-4]. When yeast cells were treated with hydroxyurea (HU) to block DNA synthesis and induce replication stress, we found that Ase1, a conserved spindle midzone protein [5], appeared as two short protein isoforms in addition to the full-length protein. We further demonstrated that the short isoforms result from intragenic transcription of ASE1, which depends on the S phase checkpoint. Blocking generation of the short isoforms leads to a destabilized S phase spindle, characterized by increased spindle dynamics and frequent spindle collapse. Because the short Ase1 isoforms localize at the spindle in HU-treated cells and overexpression of the short Ase1 isoforms impairs the spindle midzone localization of full-length Ase1, it is likely that the presence of short Ase1 isoforms stabilizes the spindle by antagonizing full-length Ase1. Together, our results reveal intragenic transcription as a unique mechanism to downregulate gene functions in response to DNA replication stress.
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