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.DNA damage | autophagy | ATM kinase | ATR kinase | budding yeast

The Ubiquitin SystemUbiquitin is a small 76eamino acid protein and is among the most highly conserved proteins ever described. Ubiquitin is Supported by the NIH Early Independence Award DP5-OD019800 (J.H.). Disclosures: J.H. receives royalties from Harvard Medical School related to US patent 9,201,073.The American Society for Investigative Pathology (ASIP) Cotran Early Career Investigator Award recognizes early career investigators with demonstrated excellence as an investigator with recently established or emerging independence and with a research focus leading to an improved understanding of the conceptual basis of disease. John Hanna, recipient of the ASIP 2019 Cotran Early Career Investigator Award, delivered a lecture entitled "Protein Degradation and the Pathologic Basis of Disease" on October 22, 2018, at the Pathobiology for Investigators, Students, and Academicians (PISA) meeting in Ann Arbor, MI.

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