Abstract
DNA damage in eukaryotic cells triggers the DNA damage checkpoint-mediated cell cycle arrest to allow the cells time to repair DNA before damaged chromosomes segregate, which if faulty can result in translocations and aneuploidy. If damage remains, budding yeast cells “adapt” to the damage after 9-12 hours by switching off the DNA damage checkpoint and proceeding through the cell cycle despite catastrophic genotoxic stress. In some mutants that fail to adapt, it was found that Pds1, a key mitotic regulator, was being degraded by autophagy, one of the main pathways of protein degradation in Saccharomyces cerevisiae. Autophagy is an important part of homeostasis and cellular survival under many different growing conditions and functions to degrade cellular waste such as proteins and organelles. The gene PPH3 and its potential target, HOG1, were identified in a screen as key players of a novel pathway of autophagy discovered recently by the Haber lab. This pathway known as GTA (Genotoxin- induced Targeted Autophagy) is induced as a response to DNA damage. Deleting HOG1, a mitogen-activated protein kinase (MAPK) gene involved in osmotic stress, resulted in blocked autophagy in response to DNA damage indicating that the gene is a positive regulator of GTA. We investigated the effects of deleting the genes upstream of HOG1 and determined which ones were implicated in the GTA pathway of HOG1. Our data suggests a model by which upstream regulators of HOG1 influence GTA.