Schematic diagram of NSMF-induced increase in RPA phosphorylation of ATR under DNA replication stress.
[정보통신신문=박남수기자] A team led by professors Lee Ja-il, Kim Hong-tae, and Choi Jang-hyeon of the Department of Life Sciences at the Ulsan Institute of Science and Technology (UNIST) revealed the process by which NSMF protein solves problems that occur when DNA replication is stressed.
NSMF protein is a protein that is mainly active in the brain and is involved in the development and movement of neurons related to growth and reproductive hormone secretion and olfaction. Failure of this protein to function normally can result in rare diseases such as hypogonadism and Kallmann syndrome with loss of smell.
The research team paid attention to the NSMF protein to relieve DNA replication stress. In proteins whose replication is stopped by DNA replication stress, the DNA structure unwinds from a double helix to a single helix. A protein called ‘replication protein A’ specifically binds to the single-stranded DNA thus formed. The combined replication protein A undergoes a phosphorylation process in which a phosphate group composed of phosphorus and oxygen is chemically attached. Phosphorylated replication protein A brings proteins that relieve replication stress to the site where replication has stopped, allowing them to resume normal activity.
On the other hand, replication protein A can bind to single-stranded DNA in weak and strong forms. The NSMF protein drops some of the weakly bound copying protein A and converts the remaining protein into a stronger form. In particular, since ATR, a phosphorylated protein, phosphorylates only strongly bound proteins, phosphorylation is rapidly amplified due to replication protein A, which is changed into a strong form by NSMF. The research team confirmed that DNA replication stress is resolved more quickly through this working principle.
Lee Ja-il, a professor at the Department of Life Sciences, said, “This study will contribute to the treatment of cancer, neurological diseases, and aging-related diseases by identifying the molecular mechanism related to DNA replication resolution.” , it seems that the discovery of a clue to solve this problem has been recognized worldwide.”
First author Yujin Kang, Ph.D. student researcher, said, “Since NSMF is closely related to Kallmann syndrome, we expect it to contribute to the treatment of this disease.”
This research, which is related to nucleic acids such as DNA and RNA, was published online on June 28 in Nucleic Acids Research, a renowned international journal. The research was carried out with the support of the Samsung Future Technology Foundation project, the basic science research laboratory and mid-level project support project promoted by the National Research Foundation of the Ministry of Science and ICT.
2023-07-13 06:57:00
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