RAD51 can inhibit PDGF-B-induced gliomagenesis and genomic instability
| Autor: | Maria Jasin, Hildur R. Helgadottir, Pernilla Roswall, Sanna-Maria Hede, Nanna Lindberg, Monica Nistér, Daniel Bråsäter, Lene Uhrbom, Ulrica K. Westermark, Anders Zetterberg |
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| Rok vydání: | 2011 |
| Předmět: |
Genome instability
DNA Replication Cancer Research DNA Repair DNA repair DNA damage Cellular differentiation Blotting Western Green Fluorescent Proteins RAD51 Mice Transgenic Biology medicine.disease_cause Genomic Instability Immunoenzyme Techniques Mice medicine Animals Humans Homologous Recombination Cells Cultured Cell Proliferation Mice Knockout Hyperplasia Brain Neoplasms Stem Cells DNA replication Brain Cell Differentiation Glioma Proto-Oncogene Proteins c-sis Fibroblasts Flow Cytometry enzymes and coenzymes (carbohydrates) Oncology Basic and Translational Investigations Cancer research ADP-Ribosylation Factor 1 Neurology (clinical) Rad51 Recombinase Homologous recombination Carcinogenesis Chickens DNA Damage |
| Zdroj: | Neuro-oncology. 13(12) |
| ISSN: | 1523-5866 |
| Popis: | Faithful replication and DNA repair are vital for maintenance of genome integrity. RAD51 is a central protein in homologous recombination repair and during replication, when it protects and restarts stalled replication forks. Aberrant RAD51 expression occurs in glioma, and high expression has been shown to correlate with prolonged survival. Furthermore, genes involved in DNA damage response (DDR) are mutated or deleted in human glioblastomas, corroborating the importance of proper DNA repair to suppress gliomagenesis. We have analyzed DDR and genomic instability in PDGF-B–induced gliomas and investigated the role of RAD51 in glioma development. We show that PDGFB–induced gliomas display genomic instability and that co-expression of RAD51 can suppress PDGF-B– induced tumorigenesis and prolong survival. Expression of RAD51 inhibited proliferation and genomic instability of tumor cells independent of Arf status. Our results demonstrate that the RAD51 pathway can prevent glioma initiation and maintain genome integrity of induced tumors, suggesting reactivation of the RAD51 pathway as a potential therapeutic avenue. |
| Databáze: | OpenAIRE |
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