[China Tech] Local Doctors Release Two Groundbreaking Studies Solving Key Life Science Puzzles

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Researchers from Shanghai Ninth People's Hospital have unveiled two pivotal scientific breakthroughs that address long-standing core challenges in life science and biomedicine.

In the first study, the team has identified a critical evolutionary safeguard that protects human germline genome stability for the first time.

Published in the top-tier journal Vita, the research reports the discovery of SAGE1, a novel primate-specific, X-linked regulator governing cellular DNA damage responses.

Scientists have long observed that germ cells in humans and other primates exhibit significantly lower mutation rates than those of rodents such as mice. The discrepancy originates from a unique evolutionary adaptation: the SAGE1 gene exclusively exists in higher primates and is absent in rodents and other non-primate mammals.

Functioning as a rapid-response command hub at DNA damage lesions, SAGE1 is recruited to damaged sites within 30 seconds via its distinctive tandem repeat sequences. It systematically remodels DNA repair pathways through a precise three-step regulatory process, switching the cellular repair mode from the error-prone non-homologous end joining to high-fidelity homologous recombination. This functional switch substantially reduces spontaneous mutation risks in human germ cells.

Notably, cancer cells are capable of hijacking this protective mechanism to repair DNA damage induced by anti-tumor treatments, thereby developing therapeutic resistance. The findings establish SAGE1 as a promising novel therapeutic target for future cancer intervention.

The second landmark study resolves a 30-year unsolved puzzle in ribonucleoprotein biology, offering critical insights into inherited genetic disorders and cancer susceptibility.

Published in Nature Communications, the research elucidates the structural architecture and evolutionary mechanisms of human RNase MRP, an essential enzyme tightly linked to severe human diseases. RNase MRP dysfunction is responsible for cartilage-hair hypoplasia, immune deficiency disorders, and elevated cancer risk, yet its molecular working mechanism has remained elusive for three decades.

Utilizing cryo-electron microscopy, the team resolved the high-resolution structure of human RNase MRP for the first time. The study also discovered two unreported specific protein subunits, NEPRO and RPP21L, filling key gaps in the molecular composition of this fundamental ribonucleoprotein complex.

These breakthrough discoveries clarify the core functional and evolutionary principles of critical human ribonucleoprotein machinery. They also provide authoritative structural and theoretical foundations for developing targeted therapies against genetic diseases and malignant tumors.