On October 17, 2024, Prof. Meng Li’s group published an article in the "Journal of Biological Chemistry" titled "DUF99 family proteins are novel endonucleases that cleave deoxyuridine on DNA substrates". Professor Meng Li served as the corresponding author, and Jinquan Li, who was a master student from the class of 2023, was the first author. Master students Ms. Runyue Xia, Mr. Jiazheng Gu, and Mr. Wencong Huang also participated in this research. Shenzhen University is the lead institution for the publication.

The study revealed that the DUF99 protein family, which contains protein of unknown function, can specifically recognize and cleave DNA substrates containing deoxyuridine. Further, this new protein family was designated as Endonuclease dU (Endo_dU). Through phylogenetic analysis and bioinformatics analysis, the paper revealed that DUF99 proteins form an independent monophyletic group distinct from other RNase H-like nuclease proteins (Fig.1), and are frequently colocalize with that for uracil-DNA glycosylase (UDG) in halophilic archaea, suggesting that they may be involved in the DNA repair process together with UDG. Physiological and biochemical experimental results showed that Endo_dU proteins exhibit activity in cleaving single-stranded DNA containing deoxyuridine under a series of conditions, with the cleavage site located on the 3' end of deoxyuridine.

This work was supported by the National Key Research and Development Program of China (2022YFA0912200), the National Natural Science Foundation of China (32225003, 32393970, 32393971), Guangdong Major Project of Basic and Applied Basic Research (2023B0303000017), the Shenzhen Medical Research Fund (B2301005), Shenzhen University 2035 Program for Excellent Research (2022B002), and the research fund from Synthetic Biology Research Center of Shenzhen University.

Original link: https://www.jbc.org/article/S0021-9258(24)02403-7/fulltext.

Figure 1. Phylogenetic analysis of DUF99 proteins.