Study Reveals NSMF Protein’s Role in Resolving DNA Replication Stress
(Seoul = Internal and external broadcasting) – Just as humans struggle under stressful situations, a new study has found that DNA replication can also encounter various problems when under stress.
Researchers from UNIST (Ulsan National Institute of Science and Technology), led by professors Lee Jae-il, Kim Hong-tae, and Choi Jang-hyeon from the Department of Life Sciences, have recently made a breakthrough in understanding how the NSMF protein addresses the challenges that arise during stressed DNA replication.
The NSMF protein primarily functions in the brain and is involved in the development and movement of nerve cells, as well as the secretion of reproductive hormones and olfaction. When this protein fails to work properly, rare conditions such as Kallman syndrome, characterized by hypogonadism and loss of smell, can occur.
The research team focused on the NSMF protein as a potential solution to relieve DNA replication stress, which occurs when errors in the replication process halt the progression. This stress leads to the unwinding of the DNA structure from a double helix to a single helix.
During this process, a protein called ‘replication protein A’ (RPA) binds to the single-stranded DNA. A phosphorylation process then takes place, where a phosphorous group is chemically attached to the replication protein A. This phosphorylated protein A recruits another protein that helps resolve replication stress, allowing normal activation to resume.
The NSMF protein plays a crucial role in strengthening the bond between replication protein A, ultimately promoting its activation. With increased strength, the protein effectively interacts with the phosphorylated protein ‘ATR’, enabling replication to resume rapidly.
The research team successfully demonstrated that this principle efficiently resolves DNA replication stress.
Professor Lee expressed his optimism about the study’s potential contributions to cancer treatment, neurological diseases, and age-related conditions. Identifying the molecular mechanisms involved in releasing DNA replication stress can pave the way for innovative therapeutic approaches.
The research, with Ph.D. student Kang Yu-jin as the first author, received support from the Samsung Foundation for Future Technology and others. It has recently been published online in the prestigious international journal ‘Nucleic Acids Research’, with the title “Alteration of replication protein Binding on single-stranded DNA by NSMF potentiates RPA phosphorylation by ATR kinase.”
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Errors in the DNA replication process create interfering ‘stress’
The NSMF protein promotes phosphorylation by making weak proteins stronger
Contribute to the treatment of cancer, neurological and ageing-related diseases
The picture has nothing to do with the content of the article. (Photo = pixabay)
(Seoul = Internal and external broadcasting) In the same way that we do not perform well under stressful situations during work, a study has found that DNA in the body can also cause various problems in stressful situations.
UNIST (Ulsan National Institute of Science and Technology) recently announced that “a research team led by professors Lee Jae-il, Kim Hong-tae, and Choi Jang-hyeon from the Department of Life Sciences discovered the process by which the NSMF protein solve it. problems that occur when DNA replication is under stress.”
NSMF protein is a protein that is mainly active in the brain and is involved in the development and movement of nerve cells associated with growth, secretion of reproductive hormones, and olfaction.
If this protein does not function normally, it can lead to rare diseases such as Kallman syndrome with hypogonadism and loss of smell.
Mimetic diagram of the increase in RPA (replication protein A) phosphorylation of ATR by NSMF under DNA replication stress. (Photo = UNIST)
The research team targeted the NSMF protein to relieve DNA replication stress.
A phenomenon where replication is blocked by an error in the DNA replication process is called ‘DNA replication stress’, and the DNA structure of the protein that has stopped replicating because of this is unwound from a double helix to a single helix.
‘Replication protein A’ binds to single-stranded DNA, and a phosphorylation process in which a phosphorus group containing phosphorus and oxygen is chemically attached to the conjugated replication protein A takes place.
Phosphorylated replication protein A brings a protein that relieves replication stress to the site where replication has stopped, allowing it to activate normally.
The role of the NSMF protein is to separate the weakly bound replication protein A, making the remaining protein strong.
The stronger protein meets the phosphorylated protein ‘ATR’ and binds strongly to protein A replicating again, resulting in rapid phosphorylation.
The research team confirmed that DNA replication stress is quickly resolved through this principle.
(Top row from left) Professor Janghyun Choi, UNIST Department of Biological Sciences, Researcher Yeji Han.
Professor Lee said, “This study will be able to contribute to the treatment of cancer, neurological diseases, and diseases associated with aging by identifying molecular mechanisms associated with the release of DNA replication stress.”
This research, in which Ph.D. student Kang Yu-jin participated as the first author, was conducted with support from the Samsung Foundation for Future Technology, etc., and was recently published online in the international journal ‘ Nucleic Acids Research’ (Title of the paper: Alteration of replication protein Binding on single-stranded DNA by NSMF potentiates RPA phosphorylation by ATR kinase).
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