DNA Link 'Cut!' Enzyme... Operation Principle Found [Science Now]

Throughout life, living organisms constantly repeat cell division. During cell division, replication occurs, and it is important to accurately transmit genetic information. During this process, various molecular activities take place.



If DNA links do not disappear during cell division, chromosomes may be divided abnormally, which may lead to genetic problems such as cancer. A domestic joint research team has discovered how a protein that acts as the last safety device works. The



team led by Professor Anton Gartner of the Ulsan National Institute of Science and Technology (UNIST) Graduate School of Medical Science and Engineering and Research Fellow Stephane Rolland of the IBS Genome Integrity Research Group have elucidated at the molecular level how LEM-3, a protein that cuts DNA links remaining between chromosomes during cell division, works.



The LEM-3 protein concentrates on the DNA bridges remaining between daughter cells at the end of cell division and participates in cutting the bridges. [Photo = UNIST]



Cell division is the process of removing old cells and creating new cells. Billions of cells divide in our bodies every day. The intestines are replaced with new cells in 1-3 days, and the skin in 2-3 weeks.



During the division process, the genetic material, DNA, is replicated. If replication is not complete or the chromosomes are not properly separated, a connecting structure called a 'DNA bridge' remains between the two newly formed daughter cells. If this connecting link is not properly processed, chromosomal abnormalities and genetic information loss occur. This can lead to the development of cancer.



The research team discovered through previous research that the LEM-3 protein acts as a last resort to remove the DNA bridge in the latter stage of cell division. LEM-3 was observed to be located in the midbody, a narrow structure that connects the two daughter cells in the final stage of division.



If LEM-3 is deficient, the DNA bridge remains even if other DNA repair factors are present, and cell division fails. The specific mechanism of LEM-3 has not been revealed so far.



The results of this study show that the 'LEM-like region' of this protein recognizes the DNA bridge and accurately positions LEM-3 in the midbody. The 'GIY-YIG region' directly cuts the connecting link.



When a mutation occurred in the LEM-like region that acts as a guide, the LEM-3 protein moved incorrectly into the nucleus instead of staying in the cytoplasm. The DNA stored in the nucleus was unintentionally cut, and the embryo died during the development process.



Research fellow Stephane Rolland explained, "LEM-3 normally exists in the cytoplasm and acts as a 'final solution' that prevents abnormal cell division, but if it is in the wrong location, it is a risk factor that threatens the cell itself," adding, "It is like a surgeon's surgical knife."



The research was conducted using the genetic model organism Caenorhabditis elegans. The LEM-3 protein of this organism is preserved in humans in the form of a similar protein called ANKLE1.



Professor Anton Gartner explained, "ANKLE1 is known to be a gene associated with the occurrence of specific cancers such as breast cancer and colon cancer, so this discovery is expected to contribute to the development of cancer prevention and treatment strategies."



The research results ((Paper title: Functional dissection of the conserved C. elegans LEM-3/ANKLE1 nuclease reveals a critical requirement for the LEM-like and GIY-YIG domains for DNA bridge processing) were published in the international academic journal Nucleic Acids Research on April 11.





https://www.inews24.com/view/blogger/1846115

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