Regulation of DNaseY activity by actinin-alpha4 during apoptosis
| Autor: | Joy X Lei, Qing Yan Liu, Marianna Sikorska, Claudie Charlebois, Caroline Sodja, J LeBlanc, P R Walker, Dao Ly, S Hirohashi, T Yamada |
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| Rok vydání: | 2004 |
| Předmět: |
Programmed cell death
biology DNA repair Microfilament Proteins DNA replication Fluorescent Antibody Technique Apoptosis Cell Biology Base excision repair DNA Fragmentation Molecular biology DNA polymerase delta Proliferating cell nuclear antigen Electrophoresis Gel Pulsed-Field Rats Two-Hybrid System Techniques biology.protein In Situ Nick-End Labeling Animals Deoxyribonuclease I Actinin Molecular Biology Replication protein A Nucleotide excision repair |
| Zdroj: | Cell death and differentiation. 11(6) |
| ISSN: | 1350-9047 |
| Popis: | DNaseY, a Ca(2+)- and Mg(2+)-dependent endonuclease, has been implicated in apoptotic DNA degradation; however, the molecular mechanisms controlling its involvement in this process have not been fully elucidated. We have obtained evidence from yeast two-hybrid screening and coimmunoprecipitation experiments that DNaseY interacted physically with actinin-alpha4 and this interaction significantly enhanced its endonuclease activity. Accordingly, simultaneous overexpression of both proteins in PC12 cells dramatically increased the rate of apoptosis in response to teniposide' VM26. However, overexpression of DNaseY alone neither triggered apoptosis nor facilitated cell death in response to VM26 or serum deprivation. Instead, the overexpression of DNaseY increased the production of single-strand DNA breaks and evoked a profound upregulation of DNA repair pathways. Taken together, our results point to a novel regulatory mechanism of DNaseY activity and offer an explanation for why cells must first cleave key DNA repair and replication proteins before the successful execution of apoptosis. |
| Databáze: | OpenAIRE |
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