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NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer
Chun-Lung Chiu1, Caiyun G Li2, Erik Verschueren3
1Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
International Journal of Molecular Sciences
|April 13, 2023
Summary
Nuclear matrix protein NUSAP1 interacts with ILF2 to maintain RNA-DNA hybrids (R-loops) and DNA damage response in prostate cancer, offering a potential therapeutic target.
Area of Science:
- Molecular Biology
- Cancer Research
- Proteomics
Background:
- Nuclear matrix protein NUSAP1 is a prognostic biomarker in prostate cancer, linked to invasion and metastasis.
- NUSAP1 expression is regulated by E2F1 and influences cancer progression.
Purpose of the Study:
- To identify proteins interacting with NUSAP1 and elucidate its biological functions.
- To investigate NUSAP1's role in R-loop maintenance and DNA damage response.
Main Methods:
- Affinity purification coupled with mass spectrometry to identify NUSAP1 interactors.
- Co-immunoprecipitation and confocal microscopy to verify protein and RNA/DNA hybrid interactions.
- Depletion studies to assess the functional impact of NUSAP1 and ILF2.
Main Results:
- Identified 85 unique proteins interacting with NUSAP1, including ILF2 and DHX9.
- Uncovered a role for NUSAP1 in maintaining R-loops and DNA damage response via ILF2 interaction.
- Demonstrated that NUSAP1 and ILF2 mRNA levels correlate with poor outcomes in prostate adenocarcinoma.
Conclusions:
- NUSAP1 interacts with ILF2 to regulate R-loop formation and DNA damage response.
- The microtubule and charged helical domains of NUSAP1 are crucial for these interactions.
- NUSAP1 and ILF2 represent potential therapeutic targets for prostate cancer.
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