Tatdn2 Safeguards Genome Stability via R-loop Resolution in Germ Cells

Maintaining genomic integrity in germ cells is essential for fertility and species survival. However, the DNA repair mechanisms that preserve genome integrity in primordial germ cells (PGCs), which experience high levels of replication stress, remain largely unknown. Although the evolutionarily conserved nuclease TatD protein family has been implicated in multiple DNA-related processes, its in vivo functions in vertebrates have not been fully elucidated.

 

Recently, the research team led by Prof. TU Qiang at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (IGDB, CAS), revealed that Tatdn2 participates in DNA damage repair in mitotic PGCs by promoting the resolution of R-loop structures, providing new insights into the mechanisms that maintain genome stability in PGCs, as well as the physiological role of Tatdn2.

 

This study, entitled “Tatdn2 is required for DNA repair to safeguard genome stability in primordial germ cells”, was published in Nucleic Acids Research on December 18, 2025 (https://doi.org/10.1093/nar/gkaf1289).

 

Tatdn2 was identified through multi-omics datasets generated in the team’s previous work (Genome Biology, 2020). Experimental validation and cross-species analyses confirmed its conserved expression in germ cells with mitotic activity. Using medaka (Oryzias latipes) as a model, the researchers found that loss of tatdn2 leads to depletion of mitotic PGCs, resulting in all adults developing as males and losing fertility. Further investigations showed that tatdn2 knockout markedly increases R-loop accumulation and DNA damage, which subsequently triggers apoptosis in PGCs.

 

The study not only fills a critical gap in understanding how PGCs cope with replication stress but also expands the known biological functions of the TatD protein family. By linking Tatdn2 to R-loop resolution and germ cell survival, the work provides a foundation for future investigations into the role of Tatdn2 in human reproductive disorders and genome stability-related diseases.

 

This work was supported by the National Natural Science Foundation of China, the CAS Key Research Program, the CAS Project for Young Scientists in Basic Research, among others.

 

 

Contact:

Prof. TU Qiang

Institute of Genetics and Developmental Biology, Chinese Academy of Sciences

Email: qtu@genetics.ac.cn