TEX264-mediated selective autophagy directs DNA damage repair

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Updated: Jun 7, 2025

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

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Yuxia Qi1, Sho W Suzuki1

  • 1School of Biological Sciences, Nanyang Technological University, Singapore.

Trends in Biochemical Sciences
|November 16, 2024
PubMed

Insights

DNA damage can cause disease, but a new study shows lysosomes aid repair. Lysosomes degrade topoisomerase 1 cleavage complex lesions through TEX264-mediated selective autophagy, revealing a novel DNA repair pathway.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • DNA damage is a significant cause of mutations and diseases.
  • DNA repair primarily occurs in the nucleus.
  • The role of other organelles in DNA repair is less understood.

Purpose of the Study:

  • To investigate the role of lysosomes in DNA repair.
  • To identify mechanisms for clearing DNA lesions outside the nucleus.

Main Methods:

  • Utilized cell-based assays to study DNA damage and repair.
  • Investigated the role of TEX264 in DNA lesion degradation.
  • Examined the involvement of selective autophagy in DNA repair.

Main Results:

  • Demonstrated that topoisomerase 1 cleavage complex (TOP1cc) DNA lesions can be degraded in lysosomes.
  • Showed that TEX264 mediates the selective autophagy of TOP1cc lesions.
  • Identified a novel lysosomal DNA repair pathway.

Conclusions:

  • Lysosomes play a previously unrecognized role in DNA repair.
  • TEX264-mediated selective autophagy is a key mechanism for clearing TOP1cc lesions.
  • This discovery opens new avenues for understanding and treating diseases associated with DNA damage.
Keywords:
DNA repairTEX264colorectal cancergenome stabilityselective autophagytopoisomerase 1 cleavage complex

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