The use of complex platinum salts (Cis-DDP) in antitumoral therapy is well known. However the mode of action of this salt remains unknown. The present study was performed with human transformed cells in culture (WI-98-VAD), grown in the presence of Cis-DDP. The intracellular localization of platinum was studied by associating the technique of microanalysis by electronic probe (analysis by wavelength dispersion: W. D. S.) and that of fine tissue sections at low temperature: ultracryotomy. The platinum was found to be concentrated mainly in the nucleolar region.
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Proc Natl Acad Sci U S A
November 2024
State Key Laboratory of Medicinal Chemical Biology, Institute of Immunology, College of Life Sciences, Nankai University, Tianjin 300071, China.
2'-O-methylation is one of the most prevalent RNA modifications found in different RNA types. However, the identities of enzymes participating in the transfer of methyl groups are not well defined. To date, fibrillarin (FBL) is the only known small nucleolar ribonucleoprotein (snoRNP) 2'-O-methyltransferase.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, P. R. China.
Elevated ribosome biogenesis correlates with the rapid growth and progression of cancer. Targeted blockade of ribosome biogenesis induces nucleolar stress, which preferentially leads to the elimination of malignant cells. In this study, it is reported that the nucleolar protein BRIX1 is a critical regulator for the homeostasis between ribosome biogenesis and p53 activation.
View Article and Find Full Text PDFBiomedicines
July 2024
School of Biological Sciences, Queen's University Belfast, Belfast BT9 5DL, UK.
While genotoxic chemotherapeutic agents are among the most effective tools to combat cancer, they are often associated with severe adverse effects caused by indiscriminate DNA damage in non-tumor tissue as well as increased risk of secondary carcinogenesis. This study builds on our previous work demonstrating that the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 elicits a non-canonical DNA damage response and our discovery of a critical role for Topoisomerase 2α (Top2α) in the initiation of Pol I-dependent transcription. Here, we identify Top2α as a mediator of CX-5461 response in the murine Eµ- B lymphoma model whereby sensitivity to CX-5461 is dependent on cellular Top2α expression/activity.
View Article and Find Full Text PDFbioRxiv
January 2024
Department of Neurology and Jungers Center for Neurosciences Research, Oregon Health and Science University, Portland, OR, USA.
Although an increased risk of the skin cancer melanoma in people with Parkinson's Disease (PD) has been shown in multiple studies, the mechanisms involved are poorly understood, but increased expression of the PD-associated protein alpha-synuclein (αSyn) in melanoma cells may be important. Our previous work suggests that αSyn can facilitate DNA double-strand break (DSB) repair, promoting genomic stability. We now show that αSyn is preferentially enriched within the nucleolus in the SK-MEL28 melanoma cell line, where it colocalizes with DNA damage markers and DSBs.
View Article and Find Full Text PDFNat Commun
November 2023
The Mina and Everard Goodman Faculty of Life Sciences and Advanced and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
Trypanosomes are protozoan parasites that cycle between insect and mammalian hosts and are the causative agent of sleeping sickness. Here, we describe the changes of pseudouridine (Ψ) modification on rRNA in the two life stages of the parasite using four different genome-wide approaches. CRISPR-Cas9 knock-outs of all four snoRNAs guiding Ψ on helix 69 (H69) of the large rRNA subunit were lethal.
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