A pathway of targeted autophagy is induced by DNA damage in budding yeast.
Autophagy plays a central role in the DNA damage response (DDR) by controlling the levels of various DNA repair and checkpoint proteins; however, how the DDR communicates with the autophagy pathway remains unknown. Using budding yeast, we demonstrate that global genotoxic damage or even a single unrepaired double-strand break (DSB) ... initiates a previously undescribed and selective pathway of autophagy that we term genotoxin-induced targeted autophagy (GTA). GTA requires the action primarily of Mec1/ATR and Rad53/CHEK2 checkpoint kinases, in part via transcriptional up-regulation of central autophagy proteins. GTA is distinct from starvation-induced autophagy. GTA requires Atg11, a central component of the selective autophagy machinery, but is different from previously described autophagy pathways. By screening a collection of ∼6,000 yeast mutants, we identified genes that control GTA but do not significantly affect rapamycin-induced autophagy. Overall, our findings establish a pathway of autophagy specific to the DNA damage response.
Mesh Terms:
Autophagy, Autophagy-Related Proteins, Cell Cycle Proteins, Checkpoint Kinase 2, DNA Breaks, Double-Stranded, DNA Damage, DNA Repair, DNA, Fungal, Intracellular Signaling Peptides and Proteins, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Vesicular Transport Proteins
Autophagy, Autophagy-Related Proteins, Cell Cycle Proteins, Checkpoint Kinase 2, DNA Breaks, Double-Stranded, DNA Damage, DNA Repair, DNA, Fungal, Intracellular Signaling Peptides and Proteins, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Vesicular Transport Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Dec. 14, 2016
PubMed ID: 28154131
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