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Lookup NU author(s): Dr Graeme Hewitt, Professor Viktor KorolchukORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2016 The Authors. (Macro)Autophagy is a catabolic pathway that delivers excess, aggregated, or damaged proteins and organelles to lysosomes for degradation. Autophagy is activated in response to numerous cellular stressors such as increased levels of reactive oxygen species (ROS) and low levels of cellular nutrients as well as DNA damage. Although autophagy occurs in the cytoplasm, its inhibition leads to accumulation of DNA damage and genomic instability. In the past few years, our understanding of the interplay between autophagy and genomic stability has greatly increased. In this review we summarize these recent advances in understanding the molecular mechanisms linking autophagy to DNA repair. Recent studies have demonstrated the turnover of nuclear components such as nuclear lamina, chromatin, and DNA by autophagy and suggest that it plays an important role in maintaining genomic stability.Loss/inhibition of autophagy gives rise to reduced DNA damage repair and increased cell death in response to genotoxic stress.The accumulation of the autophagy receptor protein p62/SQSTM1 that results from inhibition/loss of autophagy leads to inhibition of double-strand break (DSB) repair through homologous recombination (HR).Recently, progress has been made in unraveling the molecular mechanisms linking p62 and DSB repair. Nuclear p62 dampens HR through the inhibition of RNF168-mediated chromatin ubiquitination as well as targeting the HR proteins RAD51 and filamin A for degradation via the proteasome.
Author(s): Hewitt G, Korolchuk VI
Publication type: Article
Publication status: Published
Journal: Trends in Cell Biology
Year: 2016
Volume: 27
Issue: 5
Pages: 340-351
Print publication date: 01/05/2017
Online publication date: 21/12/2016
Acceptance date: 02/04/2016
Date deposited: 11/05/2017
ISSN (print): 0962-8924
ISSN (electronic): 1879-3088
Publisher: Elsevier Ltd
URL: http://doi.org/10.1016/j.tcb.2016.11.011
DOI: 10.1016/j.tcb.2016.11.011
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