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Updated: Mar 30, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
The RNA Splicing Response to DNA Damage
Lulzim Shkreta1, Benoit Chabot2
1Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada. lulzim.shkreta@usherbrooke.ca.
Abstract:
The number of factors known to participate in the DNA damage response (DDR) has expanded considerably in recent years to include splicing and alternative splicing factors. While the binding of splicing proteins and ribonucleoprotein complexes to nascent transcripts prevents genomic instability by deterring the formation of RNA/DNA duplexes, splicing factors are also recruited to, or removed from, sites of DNA damage. The first steps of the DDR promote the post-translational modification of splicing factors to affect their localization and activity, while more downstream DDR events alter their expression. Although descriptions of molecular mechanisms remain limited, an emerging trend is that DNA damage disrupts the coupling of constitutive and alternative splicing with the transcription of genes involved in DNA repair, cell-cycle control and apoptosis. A better understanding of how changes in splice site selection are integrated into the DDR may provide new avenues to combat cancer and delay aging.
Insights
DNA damage response (DDR) involves splicing factors that regulate gene expression. Understanding how DNA damage affects splicing offers new strategies for cancer therapy and aging research.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The DNA damage response (DDR) traditionally involves DNA repair pathways.
- Recent findings implicate splicing factors in maintaining genomic stability.
- Splicing factors interact with nascent transcripts to prevent RNA/DNA duplex formation.
Purpose of the Study:
- To explore the role of splicing factors in the DDR.
- To understand how DNA damage impacts splicing and gene expression.
- To identify potential therapeutic targets for cancer and aging.
Main Methods:
- Investigating the recruitment and removal of splicing factors at DNA damage sites.
- Analyzing post-translational modifications of splicing factors during DDR.
- Examining alterations in splicing factor expression in response to DNA damage.
- Studying the disruption of splicing-transcription coupling in DDR.
Main Results:
- Splicing factors are dynamically regulated during the DDR.
- Post-translational modifications affect splicing factor localization and activity.
- Downstream DDR events lead to changes in splicing factor expression.
- DNA damage disrupts the coordination between splicing and transcription of key genes.
Conclusions:
- Splicing factors play a crucial role in the DDR.
- Dysregulation of splicing during DNA damage impacts genes involved in repair, cell cycle, and apoptosis.
- Targeting splicing alterations in DDR presents novel therapeutic opportunities for cancer and aging.
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