TY - JOUR TI - Hsp70-associated chaperones have a critical role in buffering protein production costs AU - Farkas, Zoltán AU - Kalapis, Dorottya AU - Bódi, Zoltán AU - Szamecz, Béla AU - Daraba, Andreea AU - Almási, Karola AU - Kovács, Károly AU - Boross, Gábor AU - Pál, Ferenc AU - Horváth, Péter AU - Balassa, Tamás AU - Molnár, Csaba AU - Pettkó-Szandtner, Aladár AU - Klement, Éva AU - Rutkai, Edit AU - Szvetnik, Attila AU - Papp, Balázs AU - Pál, Csaba A2 - Wittkopp, Patricia J VL - 7 PY - 2018 DA - 2018/01/29 SP - e29845 C1 - eLife 2018;7:e29845 DO - 10.7554/eLife.29845 UR - https://doi.org/10.7554/eLife.29845 AB - Proteins are necessary for cellular growth. Concurrently, however, protein production has high energetic demands associated with transcription and translation. Here, we propose that activity of molecular chaperones shape protein burden, that is the fitness costs associated with expression of unneeded proteins. To test this hypothesis, we performed a genome-wide genetic interaction screen in baker's yeast. Impairment of transcription, translation, and protein folding rendered cells hypersensitive to protein burden. Specifically, deletion of specific regulators of the Hsp70-associated chaperone network increased protein burden. In agreement with expectation, temperature stress, increased mistranslation and a chemical misfolding agent all substantially enhanced protein burden. Finally, unneeded protein perturbed interactions between key components of the Hsp70-Hsp90 network involved in folding of native proteins. We conclude that specific chaperones contribute to protein burden. Our work indicates that by minimizing the damaging impact of gratuitous protein overproduction, chaperones enable tolerance to massive changes in genomic expression. KW - protein burden KW - genetic interaction KW - chaperone overload JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -