A pathway of targeted autophagy is induced by DNA damage in budding yeast
| Autor: | James E. Haber, Nathan Schiffmann, Robbie Loewith, Silvia G. Chuartzman, Roarke A. Kamber, Amélie Bernard, Vinay V. Eapen, Brenda Lemos, Enrich Sayas, Gonen Memisoglu, Maya Schuldiner, Vladimir Denic, Allison Mazella, Daniel J. Klionsky, Jessie Ang, David P. Waterman |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Saccharomyces cerevisiae Proteins DNA Repair DNA damage DNA repair Saccharomyces cerevisiae Vesicular Transport Proteins Autophagy-Related Proteins Cell Cycle Proteins Protein Serine-Threonine Kinases BAG3 03 medical and health sciences 0302 clinical medicine ddc:590 ddc:570 Autophagy DNA Breaks Double-Stranded DNA Fungal Checkpoint Kinase 2 Multidisciplinary biology fungi Intracellular Signaling Peptides and Proteins biology.organism_classification Cell biology body regions 030104 developmental biology PNAS Plus Signal transduction 030217 neurology & neurosurgery DNA Damage Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences, Vol. 114, No 7 (2017) pp. E1158-E1167 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1614364114 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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