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Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster

Páhi, Zoltán G. and Kovacs, Levente and Szűcs, Diána and Borsos, Barbara N. and Deák, Péter and Pankotai, Tibor (2022) Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster. Scientific Reports, 12 . Art. No. 5870. ISSN 2045-2322. PMCID PMC8990000. doi:10.1038/s41598-022-09703-x. https://resolver.caltech.edu/CaltechAUTHORS:20220407-717642084

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Abstract

Ubiquitylation is critical for preventing aberrant DNA repair and for efficient maintenance of genome stability. As deubiquitylases (DUBs) counteract ubiquitylation, they must have a great influence on many biological processes, including DNA damage response. To elucidate the role of DUBs in DNA repair in Drosophila melanogaster, systematic siRNA screening was applied to identify DUBs with a reduced survival rate following exposure to ultraviolet and X-ray radiations. As a secondary validation, we applied the direct repeat (DR)-white reporter system with which we induced site-specific DSBs and affirmed the importance of the DUBs Ovarian tumor domain-containing deubiquitinating enzyme 1 (Otu1), Ubiquitin carboxyl-terminal hydrolase 5 (Usp5), and Ubiquitin carboxyl-terminal hydrolase 34 (Usp34) in DSB repair pathways using Drosophila. Our results indicate that the loss of Otu1 and Usp5 induces strong position effect variegation in Drosophila eye following I-SceI-induced DSB deployment. Otu1 and Usp5 are essential in DNA damage-induced cellular response, and both DUBs are required for the fine-tuned regulation of the non-homologous end joining pathway. Furthermore, the Drosophila DR-white assay demonstrated that homologous recombination does not occur in the absence of Usp34, indicating an indispensable role of Usp34 in this process.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41598-022-09703-xDOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8990000/PubMed CentralArticle
ORCID:
AuthorORCID
Páhi, Zoltán G.0000-0002-3428-553X
Kovacs, Levente0000-0002-3226-3740
Borsos, Barbara N.0000-0002-5537-8612
Deák, Péter0000-0002-8849-0352
Pankotai, Tibor0000-0001-9810-5465
Additional Information:© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Received 15 November 2021. Accepted 21 March 2022. Published 07 April 2022. We thank Hajnalka Majoros and Vasiliki Pantazi for their expert help in commenting and correcting the manuscript. Open access funding provided by University of Szeged. This research was funded by National Research, Development and Innovation Office Grant GINOP-2.2.1-15-2017-00052, GINOP-2.3.2-15-2016-00032 and NKFI-FK 132080, the János Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/27/20, ÚNKP-20-5-SZTE-265 and ÚNKP-21-5-SZTE-563. Contributions. G.Z.P. and T.P. conceived the idea designed and supervised the experiments. G.Z.P., L.K., D.S. conducted all laboratory work. G.Z.P., B.N.B., P.D. and T.P. facilitated the laboratory analysis. G.Z.P., B.N.B., L.K., P.D. and T.P. prepared initial draft of the manuscript. G.Z.P., B.N.B., L.K., P.D. and T.P. were responsible for the final paper following contributions from all authors. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
University of SzegedUNSPECIFIED
National Research, Development and Innovation Office Hungary (NKFI)GINOP-2.2.1-15-2017-00052
National Research, Development and Innovation Office Hungary (NKFI)GINOP-2.3.2-15-2016-00032
National Research, Development and Innovation Office Hungary (NKFI)NKFI-FK 132080
Hungarian Academy of SciencesBO/27/20
Ministry of Human Resources (Hungary)ÚNKP-20-5-SZTE-265
Ministry of Human Resources (Hungary)ÚNKP-21-5-SZTE-563
PubMed Central ID:PMC8990000
DOI:10.1038/s41598-022-09703-x
Record Number:CaltechAUTHORS:20220407-717642084
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220407-717642084
Official Citation:Páhi, Z.G., Kovács, L., Szűcs, D. et al. Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster. Sci Rep 12, 5870 (2022). https://doi.org/10.1038/s41598-022-09703-x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114191
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:07 Apr 2022 09:58
Last Modified:13 Apr 2022 16:13

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