Abstract
Autophagy is a well-conserved mechanism by which organisms can recycle cellular components. Recent evidence suggests that autophagy may play an indispensable role in response to DNA damage. Previous data from the Haber lab support the existence of a novel pathway termed Genotoxin-induced Targeted Autophagy as a means of cells responding to DNA damage. Preliminary data as well as images from a microscopy-based screen led us to believe that Mrs6, a Rab escort protein, was involved in the GTA pathway. This was inferred from the involvement of Mrs6 in the function of the Bet2-Bet4 complex, the initial hit from the screen. Abolishing function of Mrs6 prior to the induction of DNA damage resulted in autophagy being blocked, while this was not the case when DNA damage was induced with MMS before gene function was ablated. The involvement of Mrs6 and Bet2 and Bet4 led us to a set of 7 genes with CAAX C-terminal motifs (a four amino acid sequence to which a prenyl group is added on the cysteine either by a farnesyltransferase or geranylgeranyltransferase). The 7 genes were suspected to potentially be involved in the GTA pathway from a screen. Of these, Lih1 (a putative lipase) and Vps71 (a protein involved in vacuolar protein sorting) proved to be blocked for autophagy upon addition of a DNA damaging agent. Taken together, these findings suggest that these three genes play a role as positive regulators of the GTA pathway.