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Final Published Version
Author
Kawaguchi, TetsuyaRollins, Matthew G.
Moinpour, Mahta
Morera, Andres A.
Ebmeier, Christopher C.
Old, William M.
Schwartz, Jacob C.
Affiliation
Univ Arizona, Dept Mol & Cellular BiolUniv Arizona, Dept Chem & Biochem
Issue Date
2019-11-06Keywords
TDP-43FUS
DNA damage repair
transcription
amyotrophic lateral sclerosis
frontal temporal dementia
Metadata
Show full item recordPublisher
AMER CHEMICAL SOCCitation
J. Proteome Res. 2020, 19, 1, 360-370Journal
JOURNAL OF PROTEOME RESEARCHRights
Copyright © 2019 American Chemical SocietyCollection Information
This 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 repository@u.library.arizona.edu.Abstract
The 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.Note
Open access articleISSN
1535-3893Version
Final published versionSponsors
This 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.ae974a485f413a2113503eed53cd6c53
10.1021/acs.jproteome.9b00575