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

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 activate...

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Main Authors: Sinem Demirbag-Sarikaya, Yunus Akkoc, Sıla Turgut, Secil Erbil-Bilir, Nur Mehpare Kocaturk, Joern Dengjel, Devrim Gozuacik
Format: Article
Language:English
Published: Nature Portfolio 2022-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-11704-9
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author Sinem Demirbag-Sarikaya
Yunus Akkoc
Sıla Turgut
Secil Erbil-Bilir
Nur Mehpare Kocaturk
Joern Dengjel
Devrim Gozuacik
author_facet Sinem Demirbag-Sarikaya
Yunus Akkoc
Sıla Turgut
Secil Erbil-Bilir
Nur Mehpare Kocaturk
Joern Dengjel
Devrim Gozuacik
author_sort Sinem Demirbag-Sarikaya
collection DOAJ
description 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.
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spelling doaj.art-d61b7c0fee8e497aa7ae86fc1d3a70aa2022-12-22T00:23:18ZengNature PortfolioScientific Reports2045-23222022-05-0112111110.1038/s41598-022-11704-9A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stressSinem Demirbag-Sarikaya0Yunus Akkoc1Sıla Turgut2Secil Erbil-Bilir3Nur Mehpare Kocaturk4Joern Dengjel5Devrim Gozuacik6SUNUM Nanotechnology Research and Application CenterKoç University Research Centre for Translational Medicine (KUTTAM)Koç University Research Centre for Translational Medicine (KUTTAM)SUNUM Nanotechnology Research and Application CenterSUNUM Nanotechnology Research and Application CenterDepartment of Biology, University of FribourgSUNUM Nanotechnology Research and Application CenterAbstract 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.https://doi.org/10.1038/s41598-022-11704-9
spellingShingle Sinem Demirbag-Sarikaya
Yunus Akkoc
Sıla Turgut
Secil Erbil-Bilir
Nur Mehpare Kocaturk
Joern Dengjel
Devrim Gozuacik
A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress
Scientific Reports
title A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress
title_full A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress
title_fullStr A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress
title_full_unstemmed A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress
title_short A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress
title_sort novel atg5 interaction with ku70 potentiates dna repair upon genotoxic stress
url https://doi.org/10.1038/s41598-022-11704-9
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