A prescription for ‘stress’ – the role of Hsp90 in genome stability and cellular adaptation

Changes in cell homeostasis, or cell ‘stress’, are thought to tax the ability of the Hsp90 chaperone to facilitate an array of processes critical for genome maintenance. Here, we review the current understanding of how the Hsp90 chaperone machinery ensures the function of proteins important for DNA repair, recombination, and chromosome segregation. We discuss the idea that cell stress can overload Hsp90, resulting in genomic instability that may have important implications for stress adaptation and selection. The importance of Hsp90 in genome maintenance and its limited capacity to buffer the proteome may underlie the initiation or progression of diseases such as cancer.