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 expansions but only when they are actively transcribed. These expansions correlate with slower transcription elongation caused by the ysh1 mutation. These results reveal an interplay between RNA processing and repeat-mediated genome instability, confirming the validity of our approach.
journal_name
Cell Repjournal_title
Cell reportsauthors
McGinty RJ,Puleo F,Aksenova AY,Hisey JA,Shishkin AA,Pearson EL,Wang ET,Housman DE,Moore C,Mirkin SMdoi
10.1016/j.celrep.2017.08.051subject
Has Abstractpub_date
2017-09-05 00:00:00pages
2490-2500issue
10issn
2211-1247pii
S2211-1247(17)31176-2journal_volume
20pub_type
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