Principles, Evolution, and Applications of Proximity Labeling
In 2024, Gergely Rona et al. published an article titled “CDK-independent role of D-type cyclins in regulating DNA mismatch repair” in Molecular Cell (PubMed ID: 38458201). In this study, researchers used TurboID technology to identify proteins in proximity to chromatin-binding D-type cyclins. They found that only proteins involved in the Base Excision Repair (BER) pathway significantly enriched near the chromatin after hydrogen peroxide treatment, suggesting that D-type cyclins accumulate near BER pathway proteins in response to oxidative stress. Additionally, they used TurboID to analyze changes in DNA damage-induced PCNA interactomes with or without D-type cyclins, discovering that when D-type cyclins were depleted, DNA repair proteins like MSH2, MSH3, and MSH6 were significantly enriched near PCNA. This indicated that D-type cyclins suppress the interaction between PCNA and mismatch repair (MMR) proteins under oxidative stress. This study highlights the broad applicability of TurboID technology, showing its potential in studying intracellular protein interactions independent of hydrogen peroxide. The plasmid sequences used, such as pLVX-NLS-HA-TurboID, are available at Addgene 215075.
Summary and Future Outlook
As an important tool in modern biological research, proximity labeling technology has undergone multiple iterations, significantly improving labeling efficiency and spatiotemporal resolution. With the continuous optimization of technologies like BioID and TurboID, proximity labeling has been widely applied in protein interaction studies, subcellular proteomics, and dynamic protein analysis in live cells. In the future, with the development of new tools and expanded applications, proximity labeling technology will play an even greater role in unveiling key regulatory mechanisms in life processes and in the development of novel drug targets.