Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Nov;20(11):1444-54.
doi: 10.1038/cdd.2013.103. Epub 2013 Aug 9.

Autophagy and genomic integrity

A T Vessoni  1 , E C Filippi-Chiela, C Fm Menck, G Lenz
Affiliations
Review

Autophagy and genomic integrity

A T Vessoni et al. Cell Death Differ. 2013 Nov.

Abstract

DNA lesions, constantly produced by endogenous and exogenous sources, activate the DNA damage response (DDR), which involves detection, signaling and repair of the damage. Autophagy, a lysosome-dependent degradation pathway that is activated by stressful situations such as starvation and oxidative stress, regulates cell fate after DNA damage and also has a pivotal role in the maintenance of nuclear and mitochondrial genomic integrity. Here, we review important evidence regarding the role played by autophagy in preventing genomic instability and tumorigenesis, as well as in micronuclei degradation. Several pathways governing autophagy activation after DNA injury and the influence of autophagy upon the processing of genomic lesions are also discussed herein. In this line, the mechanisms by which several proteins participate in both DDR and autophagy, and the importance of this crosstalk in cancer and neurodegeneration will be presented in an integrated fashion. At last, we present a hypothetical model of the role played by autophagy in dictating cell fate after genotoxic stress.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Overview of the genomic instability caused by autophagy impairment. Autophagy impairment leads to the accumulation of hazardous cellular components, such as dysfunctional mitochondria and toxic protein aggregates, which leads to an increase in ROS production (box i), cell cycle dynamic alterations, DNA damage and, consequently, genomic instability. Autophagy impairment also interferes with DNA repair (box ii) and removal of micronuclei (here referred to as nucleophagy (box iii), contributing to genomic instability. The molecular and cellular mechanisms involved in the role of mitophagy in the context of DNA damage are shown in Figure 2. Pathways that are involved in the crosstalk between DDR and autophagy are summarized in Figure 3 and Table 1, whereas the dual role of DDR-induced autophagy is shown on Figure 4 and Table 2
Figure 2
Figure 2
Mitochondria quality control by mitophagy in the context of DNA damage. Details of the processes are given in the main text. A, autophagosomes; L, lysosomes; AL, autophagolysosomes; MMP, mitochondrial membrane potential
Figure 3
Figure 3
Autophagy modulation in response to DNA damage response (DDR). DDR-activated signaling can result in autophagy modulation. The autophagy box represents the central autophagy regulating genes. DSB, double-strand brake; SSB, single-strand break; MMR, mismatch repair
Figure 4
Figure 4
Roles for autophagy in regulating cell fate after DNA damage. We propose that after DNA injury, autophagy can influence cell fate, supporting or impairing cell survival. As a cytoprotective mechanism, autophagy may degrade pro-apoptotic proteins and membrane permeabilized mitochondria, enhance ATP and dNTPs generation for DNA repair and also regulate cell cycle arrest. However, autophagy may favor cell death through degradation of anti-apoptotic and DNA repair-related proteins
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ljungman M. Activation of DNA damage signaling. Mutat Res. 2005;577:203–216. - PubMed
    1. Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481:287–294. - PubMed
    1. Lenz G. Endogenous anticancer mechanisms (EACMs) Front Biosci (Schol Ed) 2012;4:1017–1030. - PubMed
    1. Ljungman M. The DNA damage response-repair or despair. Environ Mol Mutagen. 2010;51:879–889. - PubMed
    1. Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27:107–132. - PubMed

Substances

LinkOut - more resources