Photocatalytic proximity labeling for the identification of G-quadruplex DNA-interacting proteins
Abstract DNA–protein interactions play an essential role in fundamental cellular biological processes. Herein, we report a photocatalytic proximity labeling approach for the broad screening of G-quadruplex (G4)-interacting proteins (G4IPs) using human telomere G4 DNA modified with a photocatalyst (Ruthenium complex or BODIPY). We confirmed efficient labeling of unwinding protein 1 (UP1), a model of G4-interacting protein, with 1-methyl-4-arylurazole (MAUra) as a labeling reagent under blue light irradiation. We applied this labeling approach to nuclear extract proteins and identified labeled proteins using quantitative proteomics analysis. Numerous unknown G4 binding protein candidates were identified. Notably, the hexokinase-1 (HK1) protein was identified as a G4IP, and its selective binding toward G4 DNA was confirmed. This finding could be used to highlight the essential subcellular G4-mediated functions of HK1. The proposed labeling approach is a promising tool for investigating the protein interactions of the higher-order structural motifs and functional nucleic acids.
Authors
- Maho Kato
- Satoru Nagatoishi (ORCID: https://orcid.org/0000-0002-0794-3963)
- Fumi Nagatsugi (ORCID: https://orcid.org/0000-0002-5526-6020)
- Kazumitsu Onizuka (ORCID: https://orcid.org/0000-0001-9713-4619)
- Keita Nakane (ORCID: https://orcid.org/0000-0002-2589-1722)
- Shinichi Sato (ORCID: https://orcid.org/0000-0002-8563-1658)
- Keishi Deguchi
- Kazuki Kuwahara (ORCID: https://orcid.org/0000-0002-3127-8676)
- Takanori Oyoshi (ORCID: https://orcid.org/0000-0003-4920-6790)
- Tatsuki Masuzawa (ORCID: https://orcid.org/0000-0001-9679-7883)
- Ahmed Mostafa Abdelhady (ORCID: https://orcid.org/0000-0002-8859-0126)
- Zhengyi Liu (ORCID: https://orcid.org/0009-0007-5313-4159)
- Jamila Abbas Osman
- Toshifumi Yamanaka
- Nodoka Mase
- Takemaru Sato
- Kouhei Tsumoto
- Mizuki Oba
Institutions
- Shizuoka University (JP)
- Al-Azhar University (EG)
- Tohoku University (JP)
- Al-Azhar University (ID)
- The University of Tokyo (JP)
- Shizuoka Institute of Science and Technology (JP)
Publication Details
- Journal
- Communications Chemistry
- Published
- 2026-08-27
- DOI
- https://doi.org/10.1038/s42004-026-02170-9
- Citations
- 3
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 6.06
Funders
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency