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Genotoxic stress triggers Scd6-dependent regulation of translation to modulate the DNA damage response

Gayatri Mohanan1, Raju Roy1,2, Hélène Malka-Mahieu3,4

  • 1Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India.

EMBO Reports
|April 24, 2025
PubMed

Insights

RNA-binding proteins Scd6 and LSM14A regulate DNA damage repair by controlling mRNA translation of key proteins. This study reveals their crucial role in the genotoxic stress response.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • The role of mRNA translation and decay in genotoxic stress response is not well understood.
  • RNA-binding proteins are involved in various cellular processes, but their specific roles in DNA damage response are still being elucidated.

Purpose of the Study:

  • To investigate the function of yeast RGG motif-containing RNA binding protein Scd6 and its human ortholog LSM14A in genotoxic stress response.
  • To identify the mechanisms by which these proteins regulate DNA damage repair pathways.

Main Methods:

  • Utilized yeast and mammalian cell models.
  • Investigated protein localization, genetic interactions, and direct mRNA interactions.
  • Assessed the impact on translation regulation and DNA repair pathways like Non-homologous end-joining (NHEJ).

Main Results:

  • Scd6 localizes to cytoplasmic puncta under genotoxic stress and interacts with SRS2 mRNA to repress its translation.
  • Scd6 and LSM14A regulate the translation of mRNAs encoding key DNA damage response proteins, including SRS2, RTEL1, and LIG4.
  • NHEJ activity is modulated by Scd6 in yeast and LSM14A in mammalian cells.

Conclusions:

  • RNA-binding proteins Scd6 and LSM14A play critical roles in the genotoxic stress response.
  • These proteins regulate DNA damage repair by controlling the translation of specific mRNAs encoding DNA repair proteins.
  • The findings uncover a novel mechanism of gene regulation in response to DNA damage.
Keywords:
DNA DamageGenotoxic StressRNA Binding ProteinRNA GranulesmRNA Translation

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