Autophagy and genomic integrity.
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.
Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
A T
AT
Vessoni
E C
EC
Filippi-Chiela
C Fm
CF
Menck
G
G
Lenz
D000818:Animals; D001343:Autophagy / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans
D004272:DNA, Mitochondrial