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 language | English (US) |
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Pages (from-to) | 360-370 |
Number of pages | 11 |
Journal | Journal of Proteome Research |
Volume | 19 |
Issue number | 1 |
DOIs | |
State | Published - Jan 3 2020 |
Keywords
- DNA damage repair
- FUS
- TDP-43
- amyotrophic lateral sclerosis
- frontal temporal dementia
- transcription
ASJC Scopus subject areas
- Biochemistry
- Chemistry(all)