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Correction published on 18 October 2016, see Biomolecules 2016, 6(4), 40.

Open AccessReview
Biomolecules 2015, 5(4), 2589-2618; doi:10.3390/biom5042589

Hsp90: A New Player in DNA Repair?

1
Department of Sciences, Roma Tre University, Viale Guglielmo Marconi 446, Roma I-00146, Italy
2
Istituto Nazionale di Biostrutture e Biosistemi, Viale Medaglie d’Oro 305, Roma I-00136, Italy
*
Author to whom correspondence should be addressed.
Academic Editors: Thomas Helleday, Wolf-Dietrich Heyer and Fumio Hanaoka
Received: 14 July 2015 / Revised: 8 September 2015 / Accepted: 10 September 2015 / Published: 16 October 2015
(This article belongs to the Special Issue DNA Damage Response)
View Full-Text   |   Download PDF [980 KB, uploaded 25 October 2016]   |  

Abstract

Heat shock protein 90 (Hsp90) is an evolutionary conserved molecular chaperone that, together with Hsp70 and co-chaperones makes up the Hsp90 chaperone machinery, stabilizing and activating more than 200 proteins, involved in protein homeostasis (i.e., proteostasis), transcriptional regulation, chromatin remodeling, and DNA repair. Cells respond to DNA damage by activating complex DNA damage response (DDR) pathways that include: (i) cell cycle arrest; (ii) transcriptional and post-translational activation of a subset of genes, including those associated with DNA repair; and (iii) triggering of programmed cell death. The efficacy of the DDR pathways is influenced by the nuclear levels of DNA repair proteins, which are regulated by balancing between protein synthesis and degradation as well as by nuclear import and export. The inability to respond properly to either DNA damage or to DNA repair leads to genetic instability, which in turn may enhance the rate of cancer development. Multiple components of the DNA double strand breaks repair machinery, including BRCA1, BRCA2, CHK1, DNA-PKcs, FANCA, and the MRE11/RAD50/NBN complex, have been described to be client proteins of Hsp90, which acts as a regulator of the diverse DDR pathways. Inhibition of Hsp90 actions leads to the altered localization and stabilization of DDR proteins after DNA damage and may represent a cell-specific and tumor-selective radiosensibilizer. Here, the role of Hsp90-dependent molecular mechanisms involved in cancer onset and in the maintenance of the genome integrity is discussed and highlighted. View Full-Text
Keywords: base excision repair; DNA damage response; DNA double strand break; DNA repair; Hsp90; Hsp90 inhibitors; mismatch repair; translation synthesis base excision repair; DNA damage response; DNA double strand break; DNA repair; Hsp90; Hsp90 inhibitors; mismatch repair; translation synthesis
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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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Pennisi, R.; Ascenzi, P.; di Masi, A. Hsp90: A New Player in DNA Repair? Biomolecules 2015, 5, 2589-2618.

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