Journal of Biological Chemistry
Volume 284, Issue 46, 13 November 2009, Pages 31945-31952
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DNA: Replication, Repair, Recombination, and Chromosome Dynamics
Cellular Redistribution of Rad51 in Response to DNA DamageNOVEL ROLE FOR Rad51C*

https://doi.org/10.1074/jbc.M109.024646Get rights and content
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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.

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This work was supported, in whole or in part, by National Institutes of Health Grants GM044772 and GM065851 (to K. L. K.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–3 and Table 1.