Rollins, Matthew G.
Morera, Andres A.
Ebmeier, Christopher C.
Old, William M.
Schwartz, Jacob C.
AffiliationUniv Arizona, Dept Mol & Cellular Biol
Univ Arizona, Dept Chem & Biochem
DNA damage repair
amyotrophic lateral sclerosis
frontal temporal dementia
MetadataShow full item record
PublisherAMER CHEMICAL SOC
CitationJ. Proteome Res. 2020, 19, 1, 360-370
JournalJOURNAL OF PROTEOME RESEARCH
RightsCopyright © 2019 American Chemical Society
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractThe RNA-binding proteins TDP-43 and FUS are tied as the thirdleading known genetic cause for amyotrophic lateral sclerosis (ALS), and TDP-43proteopathies are found in nearly all ALS patients. Both the natural function andcontribution to pathology for TDP-43 remain unclear. The intersection offunctions between TDP-43 and FUS can focus attention for those natural functionsmostly likely to be relevant to disease. Here, we compare the role played by TDP-43 and FUS, maintaining chromatin stability for dividing HEK293T cells. We alsodetermine and compare the interactomes of TDP-43 and FUS, quantitatingchanges in those before and after DNA damage. Finally, selected interactions withknown importance to DNA damage repair were validated by co-immunoprecipi-tation assays. This study uncovered TDP-43 and FUS binding to several factorsimportant to DNA repair mechanisms that can be replication-dependent,-independent, or both. These results provide further evidence that TDP-43 has an important role in DNA stability andprovide new ways that TDP-43 can bind to the machinery that guards DNA integrity in cells.
NoteOpen access article
VersionFinal published version
SponsorsThis work was funded by the National Institute of Health [NS082376] to J.C.S. and by a DARPA cooperative agreement grant [13-34-RTA-FP-007] to W.M.O. Research was also supported by the Office of the Director, National Institutes of Health of the National Institutes of Health under award number S10OD013237.