Changes to the TDP-43 and FUS Interactomes Induced by DNA Damage
| Autor: | Tetsuya Kawaguchi, William M. Old, Christopher C. Ebmeier, Andres A. Morera, Mahta Moinpour, Jacob C. Schwartz, Matthew Rollins |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
amyotrophic lateral sclerosis DNA Repair TDP-43 DNA repair DNA damage Biology frontal temporal dementia Biochemistry Article 03 medical and health sciences Transcription (biology) mental disorders medicine Humans Immunoprecipitation DNA damage repair Protein Interaction Maps Amyotrophic lateral sclerosis FUS Dna integrity 030102 biochemistry & molecular biology HEK 293 cells nutritional and metabolic diseases General Chemistry medicine.disease DNA Damage Repair nervous system diseases Chromatin Cell biology DNA-Binding Proteins HEK293 Cells 030104 developmental biology RNA-Binding Protein FUS transcription DNA Damage |
| Zdroj: | Journal of Proteome Research |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.9b00575 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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