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Changes to the TDP43 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 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Jacob Schwartz

PROVIDER: MSV000084486 | MassIVE | Tue Oct 22 12:06:00 BST 2019

SECONDARY ACCESSION(S): PXD015972

REPOSITORIES: MassIVE

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