Cellular redistribution of Rad51 in response to DNA damage: novel role for Rad51C.
Department of Biochemistry and Molecular Pharmacology
Life Sciences | Medicine and Health Sciences
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.
Gildemeister, O.G., Sage, J.M. and Knight, K.L. (2009) Cellular Redistribution of Rad51 in Response to DNA Damage: Novel Role for Rad51C. J. Biol. Chem. 284, 31945-31952.
The Journal of biological chemistry
Gildemeister, Otto S.; Sage, Jay M.; and Knight, Kendall L., "Cellular redistribution of Rad51 in response to DNA damage: novel role for Rad51C." (2009). GSBS Student Publications. 1631.