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

Eapen, Vinay V., Waterman, David P., Bernard, Amélie, Schiffmann, Nathan, Sayas, Enrich, Kamber, Roarke, Lemos, Brenda, Memisoglu, Gonen, Ang, Jessie, Mazella, Allison, Chuartzman, Silvia G., Loewith, Robbie J., Schuldiner, Maya, Denic, Vladimir, Klionsky, Daniel J., Haber, James E.·2017·Proceedings of the National Academy of Sciences

Abstract

Significance: The DNA damage response (DDR) is a well-orchestrated and tightly regulated process. The DDR pathway does not act in isolation; indeed, evidence of cross-talk between the DDR and numerous signaling pathways affecting cytoskeletal integrity, nutrient sensing, and autophagy has been demonstrated. In this paper, we report that the DDR induces a distinct pathway of autophagy: genotoxin-induced targeted autophagy (GTA). GTA requires the action of the checkpoint kinases Mec1/ATR, Tel1/ATM, and Rad53/CHEK2. Rad53 mediates the transcriptional up-regulation of autophagy genes via negative regulation of the repressor Rph1/KDM4. GTA requires components of the selective autophagy machinery and is distinct from canonical autophagy pathways. A genome-wide screen for GTA modulators identifies genes required for genotoxin-induced autophagy and starvation-induced autophagy.

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Metadata

Authors
Eapen, V. V., Waterman, D. P., Bernard, A., Schiffmann, N., Sayas, E., Kamber, R., Lemos, B., Memisoglu, G., Ang, J., Mazella, A., Chuartzman, S. G., Loewith, R. J., Schuldiner, M., Denic, V., Klionsky, D. J., & Haber, J. E.
Affiliations
  • Department of Biology, Brandeis University, Waltham, MA 02454;
  • Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;
  • Department of Molecular Genetics, Weizmann Institute of Sciences, Rehovot, Israel 7610001;
  • Department of Molecular Biology, University of Geneva, CH-1211 Geneva 4, Switzerland;
  • Molecular and Cell Biology, Harvard University, Cambridge, MA 02138
Venue
Proceedings of the National Academy of Sciences
Published
2017-02-02
Volume
114
Issue
7
ISSN
  • 0027-8424
  • 1091-6490
Cited by
62
References
7
Language
en
Funders
  • HHS | National Institutes of Health (GM61766, GM053396, T32 GM007122)
  • HHS | NIH | National Institute of General Medical Sciences (GM20056)
  • United States-Israel Binational Science Foundation (2013101)

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