TRIM26 Maintains Cell Survival in Response to Oxidative Stress through Regulating DNA Glycosylase Stability


Konis, Sifaddin MR, Hughes, Jonathan R and Parsons, Jason L ORCID: 0000-0002-5052-1125 (2022) TRIM26 Maintains Cell Survival in Response to Oxidative Stress through Regulating DNA Glycosylase Stability. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (19). 11613-.

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Abstract

Oxidative DNA base lesions in DNA are repaired through the base excision repair (BER) pathway, which consequently plays a vital role in the maintenance of genome integrity and in suppressing mutagenesis. 8-oxoguanine DNA glycosylase (OGG1), endonuclease III-like protein 1 (NTH1), and the endonuclease VIII-like proteins 1-3 (NEIL1-3) are the key enzymes that initiate repair through the excision of the oxidized base. We have previously identified that the E3 ubiquitin ligase tripartite motif 26 (TRIM26) controls the cellular response to oxidative stress through regulating both NEIL1 and NTH1, although its potential, broader role in BER is unclear. We now show that TRIM26 is a central player in determining the response to different forms of oxidative stress. Using siRNA-mediated knockdowns, we demonstrate that the resistance of cells to X-ray radiation and hydrogen peroxide generated as a consequence of <i>trim26</i> depletion can be reversed through suppression of selective DNA glycosylases. In particular, a knockdown of <i>neil1</i> or <i>ogg1</i> can enhance sensitivity and DNA repair rates in response to X-rays, whereas a knockdown of <i>neil1</i> or <i>neil3</i> can produce the same effect in response to hydrogen peroxide. Our study, therefore, highlights the importance of TRIM26 in balancing cellular DNA glycosylase levels required for an efficient BER response.

Item Type: Article
Uncontrolled Keywords: DNA damage, DNA repair, OGG1, NEIL1, NTH1, TRIM26, ubiquitin
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 11 Nov 2022 10:35
Last Modified: 22 Jul 2023 08:23
DOI: 10.3390/ijms231911613
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3166156
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