RRC ID 70372
著者 Páhi ZG, Kovács L, Szűcs D, Borsos BN, Deák P, Pankotai T.
タイトル Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster.
ジャーナル Sci Rep
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.
巻・号 12(1)
ページ 5870
公開日 2022-4-7
DOI 10.1038/s41598-022-09703-x
PII 10.1038/s41598-022-09703-x
PMID 35393473
PMC PMC8990000
MeSH Animals DNA Repair* Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / metabolism Hydrolases / metabolism Ubiquitin / metabolism Ubiquitin-Specific Proteases* / genetics Ubiquitin-Specific Proteases* / metabolism Ubiquitination
IF 3.998
リソース情報
ショウジョウバエ DGRC#125130 12743R-3 1950R-2