Replication protein A is required for etoposide-induced assembly of MRE11/RAD50/NBS1 complex repair foci

Jacob G. Robison, John Bissler, Kathleen Dixon

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2408-2416
Number of pages9
JournalCell Cycle
Volume6
Issue number19
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

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Replication Protein A
Etoposide
DNA Damage
Activity Cycles
Double-Stranded DNA Breaks
Cell Cycle Checkpoints
DNA Repair
Small Interfering RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Replication protein A is required for etoposide-induced assembly of MRE11/RAD50/NBS1 complex repair foci. / Robison, Jacob G.; Bissler, John; Dixon, Kathleen.

In: Cell Cycle, Vol. 6, No. 19, 01.10.2007, p. 2408-2416.

Research output: Contribution to journalArticle

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