Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage

Tetsuya Kawaguchi, Matthew G. Rollins, Mahta Moinpour, Andres A. Morera, Christopher C. Ebmeier, William M. Old, Jacob C. Schwartz

Research output: Contribution to journalArticle

Abstract

The RNA-binding proteins TDP-43 and FUS are tied as the third leading known genetic cause for amyotrophic lateral sclerosis (ALS), and TDP-43 proteopathies are found in nearly all ALS patients. Both the natural function and contribution to pathology for TDP-43 remain unclear. The intersection of functions between TDP-43 and FUS can focus attention for those natural functions mostly 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 also determine and compare the interactomes of TDP-43 and FUS, quantitating changes in those before and after DNA damage. Finally, selected interactions with known importance to DNA damage repair were validated by co-immunoprecipitation assays. This study uncovered TDP-43 and FUS binding to several factors important 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 and provide new ways that TDP-43 can bind to the machinery that guards DNA integrity in cells.

Original languageEnglish (US)
JournalJournal of Proteome Research
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Amyotrophic Lateral Sclerosis
DNA Repair
DNA Damage
RNA-Binding Proteins
DNA
Immunoprecipitation
Chromatin
Pathology
Guards (shields)
Repair
Assays

Keywords

  • amyotrophic lateral sclerosis
  • DNA damage repair
  • frontal temporal dementia
  • FUS
  • TDP-43
  • transcription

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Kawaguchi, T., Rollins, M. G., Moinpour, M., Morera, A. A., Ebmeier, C. C., Old, W. M., & Schwartz, J. C. (Accepted/In press). Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage. Journal of Proteome Research. https://doi.org/10.1021/acs.jproteome.9b00575

Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage. / Kawaguchi, Tetsuya; Rollins, Matthew G.; Moinpour, Mahta; Morera, Andres A.; Ebmeier, Christopher C.; Old, William M.; Schwartz, Jacob C.

In: Journal of Proteome Research, 01.01.2019.

Research output: Contribution to journalArticle

Kawaguchi, Tetsuya ; Rollins, Matthew G. ; Moinpour, Mahta ; Morera, Andres A. ; Ebmeier, Christopher C. ; Old, William M. ; Schwartz, Jacob C. / Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage. In: Journal of Proteome Research. 2019.
@article{720f1dfbf7794d3fa2a52e2627caff91,
title = "Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage",
abstract = "The RNA-binding proteins TDP-43 and FUS are tied as the third leading known genetic cause for amyotrophic lateral sclerosis (ALS), and TDP-43 proteopathies are found in nearly all ALS patients. Both the natural function and contribution to pathology for TDP-43 remain unclear. The intersection of functions between TDP-43 and FUS can focus attention for those natural functions mostly 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 also determine and compare the interactomes of TDP-43 and FUS, quantitating changes in those before and after DNA damage. Finally, selected interactions with known importance to DNA damage repair were validated by co-immunoprecipitation assays. This study uncovered TDP-43 and FUS binding to several factors important 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 and provide new ways that TDP-43 can bind to the machinery that guards DNA integrity in cells.",
keywords = "amyotrophic lateral sclerosis, DNA damage repair, frontal temporal dementia, FUS, TDP-43, transcription",
author = "Tetsuya Kawaguchi and Rollins, {Matthew G.} and Mahta Moinpour and Morera, {Andres A.} and Ebmeier, {Christopher C.} and Old, {William M.} and Schwartz, {Jacob C.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1021/acs.jproteome.9b00575",
language = "English (US)",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",

}

TY - JOUR

T1 - Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage

AU - Kawaguchi, Tetsuya

AU - Rollins, Matthew G.

AU - Moinpour, Mahta

AU - Morera, Andres A.

AU - Ebmeier, Christopher C.

AU - Old, William M.

AU - Schwartz, Jacob C.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The RNA-binding proteins TDP-43 and FUS are tied as the third leading known genetic cause for amyotrophic lateral sclerosis (ALS), and TDP-43 proteopathies are found in nearly all ALS patients. Both the natural function and contribution to pathology for TDP-43 remain unclear. The intersection of functions between TDP-43 and FUS can focus attention for those natural functions mostly 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 also determine and compare the interactomes of TDP-43 and FUS, quantitating changes in those before and after DNA damage. Finally, selected interactions with known importance to DNA damage repair were validated by co-immunoprecipitation assays. This study uncovered TDP-43 and FUS binding to several factors important 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 and provide new ways that TDP-43 can bind to the machinery that guards DNA integrity in cells.

AB - The RNA-binding proteins TDP-43 and FUS are tied as the third leading known genetic cause for amyotrophic lateral sclerosis (ALS), and TDP-43 proteopathies are found in nearly all ALS patients. Both the natural function and contribution to pathology for TDP-43 remain unclear. The intersection of functions between TDP-43 and FUS can focus attention for those natural functions mostly 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 also determine and compare the interactomes of TDP-43 and FUS, quantitating changes in those before and after DNA damage. Finally, selected interactions with known importance to DNA damage repair were validated by co-immunoprecipitation assays. This study uncovered TDP-43 and FUS binding to several factors important 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 and provide new ways that TDP-43 can bind to the machinery that guards DNA integrity in cells.

KW - amyotrophic lateral sclerosis

KW - DNA damage repair

KW - frontal temporal dementia

KW - FUS

KW - TDP-43

KW - transcription

UR - http://www.scopus.com/inward/record.url?scp=85076241926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076241926&partnerID=8YFLogxK

U2 - 10.1021/acs.jproteome.9b00575

DO - 10.1021/acs.jproteome.9b00575

M3 - Article

C2 - 31693373

AN - SCOPUS:85076241926

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

ER -