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The Intermediate Filament Synemin Regulates Non-Homologous End Joining in an ATM-Dependent Manner

Sara Sofia Deville1,2, Anne Vehlow1,3,4, Sarah Förster1,2

  • 1OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.

Cancers
|July 2, 2020
PubMed

Insights

This study identifies synemin, an intermediate filament protein, as a key regulator of DNA repair in head and neck cancer. Synemin influences DNA repair processes, offering new therapeutic targets for cancer treatment resistance.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Cancer treatment resistance is a complex issue, with DNA repair pathways being a significant factor.
  • While DNA repair is primarily nuclear, the influence of extra-nuclear factors on DNA damage response remains unclear.

Purpose of the Study:

  • To identify novel proteins involved in DNA repair.
  • To investigate the role of extra-nuclear cues in DNA damage response.
  • To explore potential therapeutic targets for overcoming cancer treatment resistance.

Main Methods:

  • High-throughput RNA interference (RNAi)-based screening was employed.
  • Three-dimensionally cultured head and neck squamous cell carcinoma (HNSCC) cells were used.
  • Protein complex formation and DNA repair mechanisms were analyzed.

Main Results:

  • Novel focal adhesion proteins, including the intermediate filament protein synemin, were identified as regulators of DNA repair.
  • Synemin was found to critically regulate the non-homologous end joining DNA repair pathway.
  • Synemin forms a complex with DNA-PKcs, influencing DNA repair upstream in an ATM-dependent manner.

Conclusions:

  • Synemin plays a crucial role in the DNA damage response.
  • Intermediate filament proteins can act as co-regulators of nuclear events like DNA repair.
  • This discovery provides a new understanding of cancer treatment resistance and potential therapeutic strategies.
Keywords:
ATMDNA repairDNA-PKcsHNSCCNHEJradiosensitivitysynemin

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