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When Endoplasmic Reticulum Proteostasis Meets the DNA Damage Response.

Matías González-Quiroz1, Alice Blondel2, Alfredo Sagredo3

  • 1Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health, and Metabolism (GERO), University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1242, Chemistry, Oncogenesis, Stress, and Signaling Laboratory, Université of Rennes 1, Rennes, France; Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France.

Trends in Cell Biology
|October 10, 2020
PubMed
Summary

Maintaining cellular health involves integrating the unfolded protein response (UPR) and DNA damage response (DDR). Disruptions in these pathways are linked to aging and diseases, including cancer, with emerging evidence of crosstalk.

Keywords:
ATMDNA damage responseIRE1αPERKproteostasisunfolded protein response

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Proteome and genome integrity are crucial for cellular function and organismal health.
  • The unfolded protein response (UPR) maintains endoplasmic reticulum homeostasis.
  • The DNA damage response (DDR) preserves genome stability.

Purpose of the Study:

  • To explore the signaling crosstalk between UPR and DDR.
  • To investigate the role of UPR-DDR interactions in cancer biology.

Main Methods:

  • Review of existing literature on UPR and DDR signaling.
  • Analysis of studies investigating the interplay between these two pathways.
  • Discussion of the implications for disease, particularly cancer.

Main Results:

  • UPR and DDR are critical adaptive mechanisms.
  • Alterations in UPR and DDR are implicated in aging and various pathologies.
  • Emerging evidence highlights a signaling crosstalk between UPR and DDR.

Conclusions:

  • The integration of UPR and DDR is essential for maintaining cellular integrity.
  • Understanding UPR-DDR crosstalk offers insights into aging and disease pathogenesis.
  • Targeting UPR-DDR interactions may present novel therapeutic strategies for cancer.