A Defective mRNA Cleavage and Polyadenylation Complex Facilitates Expansions of Transcribed (GAA)_n Repeats Associated with Friedreich's Ataxia.

ABSTRACT: Expansions of microsatellite repeats are responsible for numerous hereditary diseases in humans, including myotonic dystrophy and Friedreich's ataxia. Whereas the length of an expandable repeat is the main factor determining disease inheritance, recent data point to genomic trans modifiers that can impact the likelihood of expansions and disease progression. Detection of these modifiers may lead to understanding and treating repeat expansion diseases. Here, we describe a method for the rapid, genome-wide identification of trans modifiers for repeat expansion in a yeast experimental system. Using this method, we found that missense mutations in the endoribonuclease subunit (Ysh1) of the mRNA cleavage and polyadenylation complex dramatically increase the rate of (GAA)_n repeat expa

SUBMITTER: McGinty RJ 

PROVIDER: S-EPMC5658003 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature