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Int. J. Mol. Sci. 2017, 18(10), 2036; doi:10.3390/ijms18102036

Proteome Stability as a Key Factor of Genome Integrity

1
Department of Cell Biology and Biophysics, Faculty of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, 15784 Athens, Greece
2
Department of Histology and Embryology, School of Medicine, National & Kapodistrian University of Athens, 11527 Athens, Greece
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 26 July 2017 / Revised: 11 September 2017 / Accepted: 19 September 2017 / Published: 22 September 2017
(This article belongs to the Special Issue Mechanisms Leading to Genomic Instability)
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Abstract

DNA damage is constantly produced by both endogenous and exogenous factors; DNA lesions then trigger the so-called DNA damaged response (DDR). This is a highly synchronized pathway that involves recognition, signaling and repair of the damage. Failure to eliminate DNA lesions is associated with genome instability, a driving force in tumorigenesis. Proteins carry out the vast majority of cellular functions and thus proteome quality control (PQC) is critical for the maintenance of cellular functionality. PQC is assured by the proteostasis network (PN), which under conditions of proteome instability address the triage decision of protein fold, hold, or degrade. Key components of the PN are the protein synthesis modules, the molecular chaperones and the two main degradation machineries, namely the autophagy-lysosome and the ubiquitin-proteasome pathways; also, part of the PN are a number of stress-responsive cellular sensors including (among others) heat shock factor 1 (Hsf1) and the nuclear factor erythroid 2-related factor 2 (Nrf2). Nevertheless, the lifestyle- and/or ageing-associated gradual accumulation of stressors results in increasingly damaged and unstable proteome due to accumulation of misfolded proteins and/or protein aggregates. This outcome may then increase genomic instability due to reduced fidelity in processes like DNA replication or repair leading to various age-related diseases including cancer. Herein, we review the role of proteostatic machineries in nuclear genome integrity and stability, as well as on DDR responses. View Full-Text
Keywords: aggregates; autophagy; DNA damage response; genome instability; Nrf2; oxidative stress; proteostasis; proteasome aggregates; autophagy; DNA damage response; genome instability; Nrf2; oxidative stress; proteostasis; proteasome
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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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Gumeni, S.; Evangelakou, Z.; Gorgoulis, V.G.; Trougakos, I.P. Proteome Stability as a Key Factor of Genome Integrity. Int. J. Mol. Sci. 2017, 18, 2036.

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