Lamin C is important for keeping the cell's genetic material clean and tidy

2021-11-16 21:10:55 By : Ms. guohui zhou

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Researchers from the Johns Hopkins University School of Medicine said that in a study of mouse cells grown in the laboratory, they found a way to help form a structural network under the surface of the cell’s “command center” (nucleus). Protein is the key to ensuring that the DNA in it remains intact in an orderly manner. The new experiment distinguishes the role of a protein called lamin C, revealing its usefulness in the diagnosis and treatment of various genetic diseases related to DNA disintegration, such as rapid aging diseases called progeria, muscular dystrophy Heart disease associated with mutations is in these and related proteins. "The impact of these findings may extend beyond known laminar diseases, because lamin C seems to be important for genome organization. At the moment we just don't know how lamin C performs in other genomic disorders," Johns Hopkins University of Medicine Said Dr. Karen Reddy, Assistant Professor of Biochemistry at the Academy. She continued, “Many people are familiar with the idea that genetic mutations — or errors in the genetic code — can cause genetic diseases. However, highly confusing genes may be as influential as disease-causing mutations.” Reddy points out that genetic testing The organization mechanism of DNA is usually not considered, which may be an important basis for understanding genetic diseases. Reddy and her research team published their findings in Genome Biology on November 14. The nucleus of every human cell is wrapped in approximately 6 feet of tightly coiled DNA, which contains the genetic instructions for every structure and function of the body. In order to keep the cells working properly, these DNA threads must be organized into usable parts. Lamin, attached to the surface of the cell nucleus, does this by grabbing DNA fragments, keeping them separated and tidy. “Each compartment created by lamin is like a drawer of kitchen utensils, making knives, forks and spoons easy to access, as well as less commonly used items, such as putting service items aside when needed,” Reddy said. To better understand how laminin affects the way cells use and organize their DNA, Reddy and her team use fluorescent dyes to track three types of laminin-A, B, and C-through cell division, when The DNA from one cell is replicated and then divides between two progeny cells. Reddy said that although lamin B is easy to distinguish in previous studies, lamin A and lamin C have historically been regarded as duplicate proteins because they are produced by the same gene. However, there is increasing evidence that type A and type C laminins have different roles. In order to solve these problems, Reddy's research team genetically engineered mouse embryo cells to remove the gene that produces lamin B or the genes that contain both lamin A and C. The researchers then used a microscope to observe the behavior of lamin and whether the DNA of the cell nucleus remained organized during division. The research team found that the nuclear DNA in cells lacking lamin B looks almost the same as normal cell division, which means that lamin B may not be necessary for recombination of DNA after cell division. However, the nuclear DNA in cells lacking lamin A and C does not reorganize neatly and becomes entangled with the normal compartments in the nucleus. Speaking of cells lacking Lamin A and C, Reddy said: “It seems that there is a noisy party in the normally organized kitchen. Things are not in place, and the active and inactive DNA strands are mixed together. , And with the fibrin at the edge of the nucleus.” Next, the researchers used a series of specialized chemical reagents to disable lamin A or lamin C in mouse cells, allowing them to test each protein independently . Cells without lamin A seem to be able to reorganize as efficiently as normal cells after cell division. However, in cells without lamin C, the nuclear DNA organization fell into chaos again. Reddy said that one reason for this difference is revealed in the behavior of lamin C in dividing cells. Her team found that although lamin A and B quickly bind to the surface of the newly formed cell nucleus and begin to grab the DNA part, lamin C is still dispersed throughout the nucleus and retains a kind of phosphate called phosphoric acid. Special molecular tags. The researchers believe that this suggests that this modified lamin C helps guide DNA into place during the recombination process. Once the DNA is organized, lamin C loses its molecular label and binds to other laminin at the edge of the nucleus. "The different lamins and DNA are carefully arranged to get what they should be," Reddy said. The results of the study indicate that new tests can be developed to distinguish between lamin A and C and should be considered when screening for certain genetic genes. A disease involving lamin or other proteins at the edge of the nucleus. The genes encoding lamin A and C are associated with genetic diseases, including three forms of muscular dystrophy: familial partial lipodystrophy, a disease that causes abnormal distribution of adipose tissue; progeria; and several types of myocardium disease. The researchers pointed out that these results raise several new questions, including the role of laminin in organizing and regulating DNA during development. The team hopes to determine the behavior of lamin and the genome when a specific type of lamin is mutated or destroyed, because there seems to be some crosstalk between different forms of lamin. They also plan to study the cellular pathways that control laminin, especially lamin C, to further distinguish the importance of its role in controlling DNA. Reference materials: Wong X, Hoskins VE, Melendez-Perez AJ, Harr JC, Gordon M, Reddy KL. Lamin C is required to establish genome organization after mitosis. Genomic biology. 2021;22(1):305. doi: 10.1186/s13059-021-02516-7 This article is reproduced from the following materials. Note: The material may have been edited for length and content. For more information, please contact the cited source.