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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990000 | PMC |
| http://dx.doi.org/10.1038/s41598-022-09703-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Whole exome sequencing-based homologous recombination deficiency test for epithelial ovarian cancer.
J Ovarian Res
January 2025
Department of Medical Genetics, National Taiwan University Hospital, 19F, No. 8, Chung-Shan South Road, Taipei City, Taiwan.
Background: The homologous recombination deficiency (HRD) test is an important tool for identifying patients with epithelial ovarian cancer (EOC) benefit from the treatment with poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi). Using whole exome sequencing (WES)-based platform can provide information of gene mutations and HRD score; however, the clinical value of WES-based HRD test was less validated in EOC.
Methods: We enrolled 40 patients with EOC in the training cohort and 23 in the validation cohort.
Gene expression of psychiatric disorder-related kinesin superfamily proteins (Kifs) is potentiated in alternatively activated primary cultured microglia.
BMC Res Notes
January 2025
Department of Anatomy and Neuroscience, Institute of Medicine, University of Tsukuba, 1-1- 1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Objective: Reactivity of microglia, the resident cells of the brain, underlies innate immune mechanisms (e.g., injury repair), and disruption of microglial reactivity has been shown to facilitate psychiatric disorder dysfunctions.
View Article and Find Full Text PDFPARP4 deficiency enhances sensitivity to ATM inhibitor by impairing DNA damage repair in melanoma.
Cell Death Discov
January 2025
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Besides the important pathogenic mechanisms of melanoma, including BRAF-driven and immunosuppressive microenvironment, genomic instability and abnormal DNA double-strand breaks (DSB) repair are significant driving forces for its occurrence and development. This suggests investigating novel therapeutic strategies from the synthetic lethality perspective. Poly (ADP-ribose) polymerase 4 (PARP4) is known to be a member of the PARP protein family.
View Article and Find Full Text PDFDNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma.
J Nucl Med
January 2025
Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia;
Novel radiation sensitizers, including inhibitors targeting DNA damage response, have been developed to enhance the efficacy of anticancer treatments that induce DNA damage in cancer cells. Peposertib, a potent, selective, and orally administered inhibitor of DNA-dependent protein kinase, impedes the nonhomologous end-joining mechanism for DNA double-strand break (DSB) repair. We investigated radioimmunotherapy alone or with peposertib in preclinical models of renal cell carcinoma (RCC) or prostate cancer.
View Article and Find Full Text PDFTranscriptomic and Biochemical analysis of Procambarus clarkii upon exposure to Pesticides: Population-Specific responses as a sign of pollutant resistance?
Environ Res
January 2025
UMR-MARBEC, Université de Montpellier, CNRS, Ifremer, IRD, Place Eugène Bataillon, Montpellier 34095, France; Australian Rivers Institute, Griffith University, Gold Coast, 4215 Queensland, Australia. Electronic address:
The effects that anthropogenic stressors may have on modulating species' plasticity has been relatively unexplored; however, it represents a scientific frontier that may offer insights into their ability to colonize new habitats. To explore the advantage that inhabiting polluted environments may offer to invasive species, we selected the crayfish Procambarus clarkii, a species that can colonize and thrive in a wide range of aquatic environments, including heavily polluted ones. Here, we studied the molecular and physiological responses of crayfish when experimentally exposed to a pesticide mix of azoxystrobin and oxadiazon at sublethal concentrations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!