Next Article in Journal
A Mechanistic Review of Mitophagy and Its Role in Protection against Alcoholic Liver Disease
Next Article in Special Issue
Novel Implications of DNA Damage Response in Drug Resistance of Malignant Cancers Obtained from the Functional Interaction between p53 Family and RUNX2
Previous Article in Journal
Alcohol and the Intestine
Previous Article in Special Issue
Molecular Process Producing Oncogene Fusion in Lung Cancer Cells by Illegitimate Repair of DNA Double-Strand Breaks
Correction published on 18 October 2016, see Biomolecules 2016, 6(4), 40.

Open AccessReview

Hsp90: A New Player in DNA Repair?

Department of Sciences, Roma Tre University, Viale Guglielmo Marconi 446, Roma I-00146, Italy
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
Biomolecules 2015, 5(4), 2589-2618;
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)
PDF [980 KB, uploaded 25 October 2016]


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

Figure 1

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).

Share & Cite This Article

MDPI and ACS Style

Pennisi, R.; Ascenzi, P.; Di Masi, A. Hsp90: A New Player in DNA Repair? Biomolecules 2015, 5, 2589-2618.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top