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Biomolecules 2015, 5(4), 2417-2434; doi:10.3390/biom5042417

Rho GTPases: Novel Players in the Regulation of the DNA Damage Response?

Institute of Toxicology, Heinrich Heine University Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany
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Academic Editors: Wolf-Dietrich Heyer, Thomas Helleday and Fumio Hanaoka
Received: 20 August 2015 / Revised: 2 September 2015 / Accepted: 9 September 2015 / Published: 30 September 2015
(This article belongs to the Special Issue DNA Damage Response)
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Abstract

The Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the family of Ras-homologous small GTPases. It is well characterized as a membrane-bound signal transducing molecule that is involved in the regulation of cell motility and adhesion as well as cell cycle progression, mitosis, cell death and gene expression. Rac1 also adjusts cellular responses to genotoxic stress by regulating the activity of stress kinases, including c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38 kinases as well as related transcription factors. Apart from being found on the inner side of the outer cell membrane and in the cytosol, Rac1 has also been detected inside the nucleus. Different lines of evidence indicate that genotoxin-induced DNA damage is able to activate nuclear Rac1. The exact mechanisms involved and the biological consequences, however, are unclear. The data available so far indicate that Rac1 might integrate DNA damage independent and DNA damage dependent cellular stress responses following genotoxin treatment, thereby coordinating mechanisms of the DNA damage response (DDR) that are related to DNA repair, survival and cell death. View Full-Text
Keywords: DNA damage response; Rho GTPases; genotoxic stress; HMG-CoA reductase inhibitors (statins); anticancer drugs; normal tissue damage; chemical carcinogenesis DNA damage response; Rho GTPases; genotoxic stress; HMG-CoA reductase inhibitors (statins); anticancer drugs; normal tissue damage; chemical carcinogenesis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Fritz, G.; Henninger, C. Rho GTPases: Novel Players in the Regulation of the DNA Damage Response? Biomolecules 2015, 5, 2417-2434.

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