Structure-specific nucleases play crucial roles in many DNA repair pathways. They must be precisely controlled to ensure optimal repair outcomes; however, mechanisms of their regulation are not fully understood. Here, we report a fission yeast protein, Pxd1, that binds to and regulates two structure-specific nucleases: Rad16XPF-Swi10ERCC1 and Dna2-Cdc24. Strikingly, Pxd1 influences the activities of these two nucleases in opposite ways: It activates the 3' endonuclease activity of Rad16-Swi10 but inhibits the RPA-mediated activation of the 5' endonuclease activity of Dna2. Pxd1 is required for Rad16-Swi10 to function in single-strand annealing, mating-type switching, and the removal of Top1-DNA adducts. Meanwhile, Pxd1 attenuates DNA end resection mediated by the Rqh1-Dna2 pathway. Disabling the Dna2-inhibitory activity of Pxd1 results in enhanced use of a break-distal repeat sequence in single-strand annealing and a greater loss of genetic information. We propose that Pxd1 promotes proper DNA repair by differentially regulating two structure-specific nucleases.
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http://dx.doi.org/10.1371/journal.pbio.1001946 | DOI Listing |
Viruses
December 2024
Key Laboratory of Biosafety Defense (Naval Medical University), Ministry of Education, Naval Medical University (Second Military Medical University), Shanghai 200433, China.
Unlike other ubiquitin-like family members, UBL5 is structurally and functionally atypical, and a novel role in various biological processes and diseases has been discovered. UBL5 can stabilize the structure of the spliceosome, can promote post-transcriptional processing, and has been implicated in both DNA damage repair and protein unfolding reactions, as well as cellular mechanisms that are frequently exploited by viruses for their own proliferation during viral infections. In addition, UBL5 can inhibit viral infection by binding to the non-structural protein 3 of rice stripe virus and mediating its degradation.
View Article and Find Full Text PDFPharmaceutics
December 2024
Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
Osteosarcoma is a rare disease, but it is the most frequent malignant bone tumor. Primary treatment consists of preoperative MAP (methotrexate (MTX), doxorubicin and cisplatin) chemotherapy followed by surgery and adjuvant chemotherapy. Pathological response to preoperative chemotherapy is one of the most important prognostic factors, but molecular biomarkers are lacking.
View Article and Find Full Text PDFToxics
December 2024
Aquatic Contaminants Research Division, Environment and Climate Change Canada, 105 McGill, Montréal, QC H2Y 2E7, Canada.
Rare earth elements (REEs) are considered as emerging contaminants due to their use in the fabrication process of current technologies. As such, their aquatic toxicity, especially as a mixture, is not well understood, as it has been scarcely investigated. The purpose of this study was to shed light on the sublethal and lethal toxicity of a realistic mixture of five REE in .
View Article and Find Full Text PDFNutrients
December 2024
Laboratório Associado, Escola Superior de Biotecnologia, Centro de Biotecnologia e Química Fina, Universidade Católica Portuguesa, CBQF, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal.
Of all new cases of colorectal cancer, Lynch syndrome (LS) accounts for approximately 3%. This syndrome is the most common hereditary cancer syndrome and is caused by pathogenic variants in the genes responsible for DNA mismatch repair. Although the relationship between colorectal cancer risk and diet is well established, little is known regarding the influence of diet and nutritional characteristics on LS's clinical evolution.
View Article and Find Full Text PDFNutrients
December 2024
Department of Dermatology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Background/objective: Ultraviolet (UV) B radiation leads to DNA damage by generating cyclobutane pyrimidine dimers (CPDs). UVB-induced CPDs can also result in immune suppression, which is a major risk factor for non-melanoma skin cancer (NMSC). UVB-induced CPDs are repaired by nucleotide repair mechanisms (NER) mediated by xeroderma pigmentosum complementation group A (XPA).
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