MassIVE MSV000084486

Partial Public PXD015972

Changes to the TDP43 and FUS Interactomes Induced by DNA Damage

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Description

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 remains 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 either replication dependent, independent, or both. These results support recently published findings about the role TDP-43 plays in DNA repair and provide new ways that TDP-43 can bind the machinery that guard DNA integrity in cells. [doi:10.25345/C5M953] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: TDP-43 ; FUS ; DNA damage repair ; transcription ; amyotrophic lateral sclerosis ; frontal temporal dementia

Contact

Principal Investigators:
(in alphabetical order) 		Jacob Schwartz, University of Arizona, United States of America
Submitting User: jcschwartz
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