Investigation of links and crosstalk between autophagy and DNA damage responses

Sarıkaya, Sinem (2021) Investigation of links and crosstalk between autophagy and DNA damage responses. [Thesis]

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Autophagy is a well conserved intracellular degradation system that is essential for the maintenance of cellular homeostasis and protects cells from energy crisis, oxidative stress, hence DNA damage under stress conditions. Autophagy also, contributes to genomic stability by modulating various repair proteins and eliminating micronuclei carrying damaged DNA. DNA double strand breaks (DSB) are considered among the most lethal DNA damage types and repaired by two main repair systems: NHEJ and HRR. Upon DNA damage induction, autophagy activation supports HR mediated DSB repair but, impairment of autophagy causes hyperdependency on an error prone DSB repair, NHEJ. During the thesis study, we identified a novel and direct interaction between autophagy and DSB DNA repair through autophagy marker protein, ATG5 and NHEJ repair proteins. ATG5-KU70 protein interaction increased under DNA damage induction by chemotherapeutic drugs. Depletion of ATG5 protein caused delayed DSB repair through declined p-H2AX resolution. KU70 was not the target of autophagy under autophagic stimulation, which implies an autophagy independent role for ATG5-KU70 interaction. All the results indicated that KU70 is a novel interaction partner of ATG5 and this interaction is important for the repair of DSB damage under chemotherapeutic drug induced genotoxic stress.
Item Type: Thesis
Uncontrolled Keywords: DNA damage. -- DNA Repair. -- Autophagy. -- Chemotherapeutics. -- NHEJ. -- ATG5. -- KU70. -- DNA damage. -- DNA Repair.-- Autophagy. -- Chemotherapeutics.
Subjects: T Technology > TA Engineering (General). Civil engineering (General) > TA164 Bioengineering
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: IC-Cataloging
Date Deposited: 27 Dec 2021 15:28
Last Modified: 06 Jul 2022 15:00

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