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)
Pages (from-to)360-370
Number of pages11
JournalJournal of Proteome Research
Volume19
Issue number1
DOIs
StatePublished - Jan 3 2020

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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  • Cite this

    Kawaguchi, T., Rollins, M. G., Moinpour, M., Morera, A. A., Ebmeier, C. C., Old, W. M., & Schwartz, J. C. (2020). Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage. Journal of Proteome Research, 19(1), 360-370. https://doi.org/10.1021/acs.jproteome.9b00575