The repair of DNA double-strand breaks (DSBs) through homologous recombination (HR) is vital for maintaining the stability and integrity of the genome. RNA binding proteins (RBPs) intricately regulate the DNA damage repair process, yet the precise molecular mechanisms underlying their function remain incompletely understood. In this study, we highlight the pivotal role of RPS15, a representative RBP, in homologous recombination repair. Specifically, we demonstrate that RPS15 promotes DNA end resection, a crucial step in homologous recombination. Notably, we identify an interaction between RPS15 and CtIP, a key factor in homologous recombination repair. This interaction is essential for CtIP recruitment to DSB sites, subsequent RPA coating, and RAD51 replacement, all critical steps in efficient homologous recombination repair and conferring resistance to genotoxic treatments. Functionally, suppressing RPS15 expression sensitizes cancer cells to X-ray radiation and enhances the therapeutic synergistic effect of PARP1 inhibitors in breast cancer cells. In summary, our findings reveal that RPS15 promotes DNA end resection to ensure effective homologous recombination repair, suggesting its potential as a therapeutic target in cancer treatment.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1667/RADE-24-00134.1 | DOI Listing |
Front Antibiot
June 2024
Institute of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-Universität, Freiburg, Germany.
Rifamycin and its derivatives are natural products that belong to the class of antibiotic-active polyketides and have significant therapeutic relevance within the therapy scheme of tuberculosis, a worldwide infectious disease caused by . Improving the oral bioavailability of rifamycin B was achieved through semisynthetic modifications, leading to clinically effective derivatives such as rifampicin. Genetic manipulation of the rifamycin polyketide synthase gene cluster responsible for the production of rifamycin B in the strain S699 represents a promising tool to generate new rifamycins.
View Article and Find Full Text PDFFuture Oncol
January 2025
Department of Oncology, University of Turin, Division of Medical Oncology, Ordine Mauriziano Hospital, Turin, Italy.
Aims: To explore physician-reported knowledge, use, and perceptions of genetic testing for advanced ovarian cancer management.
Materials & Methods: Gynecology/oncology specialists ( = 390) in the US, Europe, Canada, Japan, and Australia completed an online survey spanning March 2021 to April 2022.
Results: Physician-reported breast cancer gene mutation (BRCAm) testing rates increased over the 2 years before the survey; most patients underwent testing in the preceding 6 months.
J Hepatobiliary Pancreat Sci
January 2025
Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.
In Japan, 5 years have passed since the initiation of precision cancer medicine, and recent data accumulation in familial pancreatic cancer (FPC) and hereditary pancreatic cancer is outstanding. Multigene germline panel tests (MGPTs) have revealed that 7%-18% of patients with pancreatic cancer (PC) harbor pathogenic germline variants (PGVs), almost equal to the levels of breast, ovarian, endometrial, and colorectal cancers, with a higher incidence in FPC (14%-26%). The majority of PGVs seen in PC patients are clinically actionable and associated with homologous recombination (HR) pathways (6%-10%, particularly BRCA1/2 in 5%-6%), and the clinical guidelines recommend or propose genetic testing for all PC patients.
View Article and Find Full Text PDFNat Cell Biol
January 2025
Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.
Double-strand breaks (DSBs) can initiate mitotic catastrophe, a complex oncosuppressive phenomenon characterized by cell death during or after cell division. Here we unveil how cell cycle-regulated DSB repair guides disparate cell death outcomes through single-cell analysis of extended live imaging. Following DSB induction in S or G2, passage of unresolved homologous recombination intermediates into mitosis promotes non-immunogenic intrinsic apoptosis in the immediate attempt at cell division.
View Article and Find Full Text PDFPLoS Genet
January 2025
Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
The synaptonemal complex (SC) is a protein-rich structure essential for meiotic recombination and faithful chromosome segregation. Acting like a zipper to paired homologous chromosomes during early prophase I, the complex is a symmetrical structure where central elements are connected on two sides by the transverse filaments to the chromatin-anchoring lateral elements. Despite being found in most major eukaryotic taxa implying a deeply conserved evolutionary origin, several components of the complex exhibit unusually high rates of sequence turnover.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!