A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress

Sinem Demirbag‑Sarikaya, Yunus Akkoc, Sila Turgut, Secil Erbil-Bilir, Nur Mehpare Kocaturk, Jörn Dengjel, Devrim Gozuacik (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

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Abstract

The maintenance of cellular homeostasis in living organisms requires a balance between anabolic and catabolic reactions. Macroautophagy (autophagy herein) is determined as one of the major catabolic reactions. Autophagy is an evolutionarily conserved stress response pathway that is activated by various insults including DNA damage. All sorts of damage to DNA potentially cause loss of genetic information and trigger genomic instability. Most of these lesions are repaired by the activation of DNA damage response following DNA repair mechanisms. Here we describe, a novel protein complex containing the autophagy protein ATG5 and the non-homologous end-joining repair system proteins. We discovered for the first time that ATG5 interacted with both Ku80 (XRCC5) and Ku70 (XRCC6). This novel interaction is facilitated mainly via Ku70. Our results suggest that this interaction is dynamic and enhanced upon genotoxic stresses. Strikingly, we identified that ATG5-Ku70 interaction is necessary for DNA repair and effective recovery from genotoxic stress. Therefore, our results are demonstrating a novel, direct, dynamic, and functional interaction between ATG5 and Ku70 proteins that plays a crucial role in DNA repair under genotoxic stress conditions.
Original languageEnglish
Article number8134
Number of pages11
JournalScientific Reports
Volume12
DOIs
Publication statusPublished - 17 May 2022

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