A role for USP9X in homologous recombination repair of DNA double strand breaks
O'Dea, Rachel
O'Dea, Rachel
Loading...
Publication Date
2020-02-11
Type
Thesis
Downloads
Citation
Abstract
In order to prevent the deleterious effects of a variety of genotoxic agents, cells have developed complex surveillance mechanisms and multiple DNA repair pathways that allow them to maintain genome integrity. The deubiquitinase Ubiquitin Specific Protease 9X (USP9X) contributes to genome stability during DNA replication and chromosome segregation. Depletion of USP9X leads to DNA double strand breaks, some of which are triggered by replication forks collapse and impaired checkpoint response. Here we identify USP9X as a novel regulator of homologous recombination (HR) DNA repair in human cells. Using a cellular HR reporter assay, irradiation induced focus formation assays and colony formation assays we show that USP9X is required for efficient HR. Mechanistically, we find that USP9X is important to sustain the expression levels of key HR factors, namely BRCA1 and RAD51 through non-canonical regulation of their mRNA abundance. Intriguingly, we find that USP9X contribution to BRCA1 and RAD51 expression and function in DSB DNA repair is not strictly reliant on its known catalytic activity. Thus, this work identifies a novel layer of regulation of HR involving USP9X and potentially identifies a catalytically independent function of USP9X.
Publisher
NUI Galway
Publisher DOI
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland