In this chapter, we focus on the role of the chaperone protein Hsp90 as a capacitor for morphological variation that is released during times of stress. Hsp90 helps to fold numerous client proteins, which constitute a veritable who's who of important signaling molecules, such as Akt, Raf, Src, chromatin-modifying proteins, nuclear hormone receptors, and kinetochore assembly proteins. We first review evidence that Hsp90 functions trans-generationally as a capacitor for morphological variation via both genetic and epigenetic means: in the former by revealing cryptic genetic variation and in the latter by generating heritable epialleles. Then we discuss two mechanisms by which altered Hsp90 function can mutate DNA: transposon mobilization, and chromosomal aneuploidy. Next, we hypothesize how beneficial cryptic epigenetic variation might be stabilized, or locked in place, by the directed DNA-level mutation of epigenetically assimilated epialleles. Finally, we describe how Hsp90 functions intra-generationally within an organism's lifetime by releasing cryptic phenotypic variation during development in a stressful environment, and how this can be hijacked during the progression of diseases such as cancer.
CITATION STYLE
Lu, X., Wang, L., Sollars, V. E., Garfinkel, M. D., & Ruden, D. M. (2013). Hsp90 as a capacitor of both genetic and epigenetic changes in the genome during cancer progression and evolution. In Stress-Induced Mutagenesis (pp. 79–101). Springer New York. https://doi.org/10.1007/978-1-4614-6280-4_5
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