Autophagy and genomic integrity

A T Vessoni1, E C Filippi-Chiela, C Fm Menck

  • 1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Insights

Autophagy, a cellular process, is crucial for maintaining genomic stability by degrading DNA damage and preventing cancer. This review explores its role in DNA repair and cell fate determination after injury.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • DNA lesions arise from endogenous and exogenous sources, triggering the DNA damage response (DDR).
  • Autophagy, a lysosome-dependent degradation pathway, responds to cellular stress and maintains genomic integrity.
  • Autophagy plays a critical role in regulating cell fate following DNA damage.

Purpose of the Study:

  • To review the evidence for autophagy's role in preventing genomic instability and tumorigenesis.
  • To discuss pathways of autophagy activation post-DNA injury and its influence on lesion processing.
  • To present a model for autophagy's function in cell fate decisions after genotoxic stress.

Main Methods:

  • Literature review of existing research on autophagy and DNA damage response.
  • Analysis of molecular mechanisms linking autophagy and DDR pathways.
  • Integration of evidence on protein involvement in both processes.

Main Results:

  • Autophagy is vital for degrading DNA damage, including micronuclei, thus preventing genomic instability.
  • Specific pathways activate autophagy following DNA injury, influencing lesion repair.
  • Crosstalk between DDR and autophagy proteins is critical in diseases like cancer and neurodegeneration.

Conclusions:

  • Autophagy is a key regulator of cellular response to DNA damage, impacting genomic stability and disease.
  • Understanding the interplay between autophagy and DDR offers insights into therapeutic strategies for cancer and neurodegenerative disorders.
  • A hypothetical model is proposed for autophagy's role in dictating cell fate after genotoxic stress.

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