Cellular Redistribution of Rad51 in Response to DNA Damage: NOVEL ROLE FOR Rad51C*
| Autor: | Gildemeister, Otto S., Sage, Jay M., Knight, Kendall L. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Cell Nucleus
Cytoplasm Infrared Rays Reverse Transcriptase Polymerase Chain Reaction Genes BRCA2 Immunoblotting Nuclear Localization Signals Active Transport Cell Nucleus DNA Neoplasm HCT116 Cells DNA-Binding Proteins Pancreatic Neoplasms enzymes and coenzymes (carbohydrates) DNA: Replication Repair Recombination and Chromosome Dynamics Humans RNA Messenger Rad51 Recombinase biological phenomena cell phenomena and immunity DNA Damage HeLa Cells Subcellular Fractions |
| Popis: | Exposure of cells to DNA-damaging agents results in a rapid increase in the formation of subnuclear complexes containing Rad51. To date, it has not been determined to what extent DNA damage-induced cytoplasmic to nuclear transport of Rad51 may contribute to this process. We have analyzed subcellular fractions of HeLa and HCT116 cells and found a significant increase in nuclear Rad51 levels following exposure to a modest dose of ionizing radiation (2 grays). We also observed a DNA damage-induced increase in nuclear Rad51 in the Brca2-defective cell line Capan-1. To address a possible Brca2-independent mechanism for Rad51 nuclear transport, we analyzed subcellular fractions for two other Rad51-interacting proteins, Rad51C and Xrcc3. Rad51C has a functional nuclear localization signal, and although we found that the subcellular distribution of Xrcc3 was not significantly affected by DNA damage, there was a damage-induced increase in nuclear Rad51C. Furthermore, RNA interference-mediated depletion of Rad51C in HeLa and Capan-1 cells resulted in lower steady-state levels of nuclear Rad51 as well as a diminished DNA damage-induced increase. Our results provide important insight into the cellular regulation of Rad51 nuclear entry and a role for Rad51C in this process. |
| Databáze: | OpenAIRE |
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