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Replication Protein A is Required for Etoposide-Induced Assembly of MRE11/RAD50/NBS1 Complex Repair Foci

Jacob G. Robison, John J. Bissler and Kathleen Dixon

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The presence of DNA damage activates a specific response cascade culminating in DNA repair activity and cell cycle checkpoints. Although the type of lesion dictates what proteins are involved in the response, replication protein A (RPA) and the Mre11/Rad50/Nbs1 complex (MRN) respond to most types of lesions. To examine the relationship of RPA and the MRN complex in DNA damage responses, we used siRNA-mediated protein depletion of RPA-p70 and Mre11. Depletion of RPA-p70 decreased the ability of cells to form phospho-Nbs1 foci and increased levels of DNA double-strand breaks (DSBs) following treatment with etoposide (ETOP). In contrast, depletion of Mre11 led to increased levels of RPA-p34 foci formation, but abrogated phospho-RPA-p34 foci formation. These data support a role for RPA as an initial signal/sensor for DNA damage that facilitates recruitment of MRN and ATM/ATR to sites of damage, where they then work together to fully activate the DNA damage response.

Authors

Jacob G. Robison

Cincinnati Children’s Hospital Medical Center; Cincinnati, Ohio

John J. Bissler

Cincinnati Children’s Hospital Medical Center; Cincinnati, Ohio

Kathleen Dixon

University of Arizona; Tucson, Arizona

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.