This article describes a novel interaction between aging and ER overload. The authors studied a dementia disease in Caenorhabdidis elegans and mice to learn how disturbed protein homeostasis contributes to disease development. They show that induction of the unfolded protein response is critical for age-related disease progression. Their results suggest that the unfolded protein response may offer a therapeutic target for dementias.
Genome Integrity and Transmission:
Emergence of DNA polymerase ε antimutators that escape error-induced extinction in yeast, pp. 751-770
Lindsey N. Williams, Alan J. Herr, and Bradley D. Preston
Mutators accelerate microbial adaptation (and mammalian oncogenesis), but the fitness cost of increased mutation imposes pressure to reduce mutation rates. In this investigation of pathways of mutator suppression, the authors show that yeast cells defective in mismatch repair and in proofreading by the primary leading-strand DNA polymerase are inviable, but escape this error-induced extinction by acquiring antimutator alleles. These findings illustrate the inherent instability of mutators and reveal multiple mechanisms of their suppression.
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Genetics Society of America