Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2017

A novel pathway of targeted autophagy is induced by DNA damage in budding yeast

Résumé

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.
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hal-03156537 , version 1 (30-12-2024)

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Vinay Eapen, David Waterman, Amélie Bernard, Nathan Schiffman, Enrich Sayas, et al.. A novel pathway of targeted autophagy is induced by DNA damage in budding yeast. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114 (7), pp.E1158-E1167. ⟨10.1073/pnas.1614364114⟩. ⟨hal-03156537⟩

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