Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response

Research output: Contribution to journalJournal articleResearchpeer-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.
Original languageEnglish
JournalMolecular Cell
Issue number2
Pages (from-to)212-25
Number of pages14
Publication statusPublished - 2012

    Research areas

  • 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

ID: 40288839