RT Journal Article
SR Electronic
T1 Genotoxin-induced transcriptional repression regulates selective protein aggregation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 116822
DO 10.1101/116822
A1 Veena Mathew
A1 Annie S. Tam
A1 Karissa L. Milbury
A1 Analise K. Hofmann
A1 Christopher S. Hughes
A1 Gregg B. Morin
A1 Christopher J. R. Loewen
A1 Peter C. Stirling
YR 2017
UL http://biorxiv.org/content/early/2017/03/15/116822.abstract
AB Upon genotoxic stress, dynamic relocalization events control DNA repair, and alterations of the transcriptome and proteome enabling stress recovery. How these events may influence one another is only partly known. Beginning with a cytological screen for genome maintenance proteins that move under stress, we find that, upon alkylation stress, the splicing factor Hsh155 localizes to both intranuclear and cytoplasmic protein quality control aggregates. Under stress, an ordered sequestration of Hsh155 occurs at nuclear and then cytoplasmic aggregates in a manner that is regulated by molecular chaperones. This dynamic behavior is preceded by a decrease in splicing efficiency. While DNA replication stress signaling is not required for Hsh155 sequestration, Hsh155 aggregation is cell cycle and TOR pathway dependent. Indeed, loss of a TORC1 regulated ribosomal protein gene transcription factor Sfp1 allows general aggregate formation but prevents Hsh155 recruitment. Together, our analyses suggest a model in which some proteins evicted from chromatin undergoing transcriptional remodeling during stress are targeted to protein quality control sites.