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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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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.

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|November 4, 2015
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Summary

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.

Keywords:
DNA damage responseR-loopsRNA binding proteinsalternative splicingchromatinpre-mRNAsignal transductionsplice site selectionsplicing factorstranscription

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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.