The First Step in Treating Various Diseases... UNIST Finds a Way to Relieve DNA Replication Stress

Ulsan National Institute of Science and Technology (UNIST) recently discovered a clue to resolving issues that occur when DNA replication stops.

This is expected to contribute to the treatment of diseases such as cancer, neurological disorders, and aging, which arise from disruptions in DNA replication.

The research team led by Professors Ja-il Lee, Hong-tae Kim, and Jang-hyun Choi from the Department of Life Sciences at UNIST elucidated the mechanism by which the NSMF protein resolves problems occurring under DNA replication stress conditions.

The NSMF protein primarily functions in the brain and is involved in the development and movement of nerve cells related to growth and reproductive hormone secretion, as well as olfaction.

If this protein does not function properly, it can lead to rare diseases such as Kallmann syndrome, which is accompanied by hypogonadism and loss of olfactory function.

According to the research team, during the process of alleviating DNA replication stress, the NSMF protein converts ‘Replication Protein A’ (RPA) into a stronger form.

Proteins stalled by DNA replication stress cause the DNA structure to unwind from a double helix into a single strand and bind to RPA.

The bound RPA undergoes phosphorylation, a chemical process where phosphate groups composed of phosphorus and oxygen attach to it. Phosphorylated RPA recruits proteins that resolve replication stress to the stalled site, enabling normal activity.

A schematic diagram of increased ATR-mediated RPA phosphorylation by NSMF under DNA replication stress.

The NSMF protein plays a role in removing some weakly bound RPA during the binding process between single-stranded DNA and RPA, converting the remaining RPA into a stronger form. The phosphorylating protein ATR only phosphorylates strongly bound proteins, so RPA transformed into a strong form by NSMF is rapidly phosphorylated. The research team confirmed that this mechanism allows DNA replication stress to be resolved more quickly.

Professor Ja-il Lee of the Department of Life Sciences explained, “This study elucidates the molecular mechanism related to the resolution of DNA replication stress and is expected to contribute to the treatment of diseases related to cancer, neurological disorders, and aging.”

Yujin Kang, a doctoral researcher and first author, said, “NSMF is closely related to Kallmann syndrome, so it is expected to contribute to the treatment of this disease.”

This research, related to nucleic acids such as DNA and RNA, was published online on June 28 in the international journal Nucleic Acids Research.

The research was conducted with support from the Samsung Future Technology Development Fund project and the Basic Science Research Laboratory and Mid-Career Research Support projects promoted by the National Research Foundation of Korea under the Ministry of Science and ICT.

This content was produced with the assistance of AI translation services.