Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response
Research output: Contribution to journal › Journal article › Research › peer-review
The regulatory networks of the DNA damage response (DDR) encompass many proteins and posttranslational modifications. Here, we use mass spectrometry-based proteomics to analyze the systems-wide response to DNA damage by parallel quantification of the DDR-regulated phosphoproteome, acetylome, and proteome. We show that phosphorylation-dependent signaling networks are regulated more strongly compared to acetylation. Among the phosphorylated proteins identified are many putative substrates of DNA-PK, ATM, and ATR kinases, but a majority of phosphorylated proteins do not share the ATM/ATR/DNA-PK target consensus motif, suggesting an important role of downstream kinases in amplifying DDR signals. We show that the splicing-regulator phosphatase PPM1G is recruited to sites of DNA damage, while the splicing-associated protein THRAP3 is excluded from these regions. Moreover, THRAP3 depletion causes cellular hypersensitivity to DNA-damaging agents. Collectively, these data broaden our knowledge of DNA damage signaling networks and highlight an important link between RNA metabolism and DNA repair.
|Number of pages||14|
|Publication status||Published - 2012|
- Cell Line, Tumor, DNA Damage, DNA Repair, DNA-Binding Proteins, HeLa Cells, Humans, Phosphoprotein Phosphatases, Phosphorylation, Proteomics, Signal Transduction, Transcription Factors, Tumor Necrosis Factor-alpha