The human DEK oncogene regulates DNA damage response signaling and repair
| العنوان: | The human DEK oncogene regulates DNA damage response signaling and repair |
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| المؤلفون: | Elisia D. Tichy, Sandy Schwemberger, John J. Bissler, Trisha Wise-Draper, Lisa Wiesmüller, James M. Wells, Monique A. Morrison, Gina Kavanaugh, George F. Babcock, Paul R. Andreassen, Lu Lu, Rachid Drissi, Susanne I. Wells, Boris Gole, Richard J. Morreale, Peter J. Stambrook |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Senescence, Programmed cell death, DNA Repair, DNA repair, DNA damage, Chromosomal Proteins, Non-Histone, Mice, Nude, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, DNA-Activated Protein Kinase, Biology, Genome Integrity, Repair and Replication, Protein Serine-Threonine Kinases, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Line, Tumor, Genetics, Animals, Humans, DNA Breaks, Double-Stranded, Poly-ADP-Ribose Binding Proteins, 030304 developmental biology, Mice, Knockout, Oncogene Proteins, 0303 health sciences, Gene knockdown, Tumor Suppressor Proteins, 3. Good health, DNA-Binding Proteins, stomatognathic diseases, 030220 oncology & carcinogenesis, Knockout mouse, Cancer cell, Cancer research, Female, Signal Transduction |
| الوصف: | The human DEK gene is frequently overexpressed and sometimes amplified in human cancer. Consistent with oncogenic functions, Dek knockout mice are partially resistant to chemically induced papilloma formation. Additionally, DEK knockdown in vitro sensitizes cancer cells to DNA damaging agents and induces cell death via p53-dependent and -independent mechanisms. Here we report that DEK is important for DNA double-strand break repair. DEK depletion in human cancer cell lines and xenografts was sufficient to induce a DNA damage response as assessed by detection of γH2AX and FANCD2. Phosphorylation of H2AX was accompanied by contrasting activation and suppression, respectively, of the ATM and DNA-PK pathways. Similar DNA damage responses were observed in primary Dek knockout mouse embryonic fibroblasts (MEFs), along with increased levels of DNA damage and exaggerated induction of senescence in response to genotoxic stress. Importantly, Dek knockout MEFs exhibited distinct defects in non-homologous end joining (NHEJ) when compared to their wild-type counterparts. Taken together, the data demonstrate new molecular links between DEK and DNA damage response signaling pathways, and suggest that DEK contributes to DNA repair. |
| اللغة: | English |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea3b1ffb35290d9d1603e68e55457f5d http://europepmc.org/articles/PMC3177200 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ea3b1ffb35290d9d1603e68e55457f5d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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