The deubiquitinase USP38 promotes NHEJ repair through regulation of HDAC1 activity and regulates cancer cell response to genotoxic insults
作者： Yongfeng Yang , Chuanzhen Yang , Tingting Li , Shuyu Yu , Tingting Gan
DOI: 10.1158/0008-5472.CAN-19-2149
关键词:
摘要: The DNA damage response (DDR) is essential for maintaining genome integrity. Mounting evidence reveals that protein modifications play vital roles in the DDR. Here, we show USP38 involved DDR by regulating activity of HDAC1. In to damage, interacted with HDAC1 and specifically removed K63-linked ubiquitin chain promoting deacetylase As a result, was able deacetylate H3K56. deletion resulted persistent focal accumulation nonhomologous end joining (NHEJ) factors at sites impaired NHEJ efficiency, causing instability sensitizing cancer cells genotoxic insults. Knockout rendered mice hypersensitive irradiation shortened survival. addition, expressed low levels certain types cancers including renal cell carcinoma, indicating dysregulation expression contributes genomic may lead tumorigenesis. summary, this study identifies critical role modulating integrity resistance insults deubiquitinating its deacetylation activity. SIGNIFICANCE: This demonstrates regulates stability mediates DNA-damaging therapy, providing insight into tumorigenesis implicating as potential target diagnosis.
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