Hidden DNA regulator links fertility and cancer

This research is led by Professor Metinori Saito, Director/Commander of the Institute of Advanced Study of Human Biology (WPI-Ashbi), University of Kyoto (also a professor at the Faculty of High Medicine), and Dr. Masharao Naganeo (then a professor at the Faculty of Medicine, currently a researcher at Ashbi and postdocontal in The Massachosts. Research in Ashbi. Biological and molecular biological nature At 10:00 am GMT (6:00 pm Standard time in Japan) on August 25, 2025.

background

Our bodies have many different cells, however they all contain the same DNA. What makes each type of cell unique is how to modify this DNA, its filling, fold and regulation. Think about the DNA as a very long piece of the chain. Inside each nucleus, about two meters of this DNA chain should be folded and stored in a smaller area of ​​human hair width. This fold is very organized, with special limits called insulation that separates different areas of DNA and control the genes that are operated or stopped. Protein complexes are a loop called Cohesins as a main player who creates these limits. It was previously believed that the cohesion complexes are present in two main forms: division cohesion (containing Stag1 or Stag2 with RAD21) and selective coordination (containing Stag3 with REC8 or Rad21L).

The bacterial cells are unique because they pass the DNA to the next generation, and are subject to significant changes in folding the DNA during development. These cells are undergoing enormous reorganization to fill the DNA during development. It is worth noting that SSCS has a unique way to regulate their DNA with unusually weak boundaries, but scientists do not yet understand how this happens.

The main results

Since the cohesion complexes contribute within the limits of the DNA, and SSCS divide the cells high before entering the measurable division, the research team decided to appoint as there are different coherent proteins in the SSCS cultivated in the laboratory, and any proteins are found in each site. They found that Rad21, which is usually with Stag1 or Stag2 in division cells, was instead a partnership with Stag3. This protein had previously thought it only operated during the mechanical division. Using an immune mass spectrum measuring (a technique that determines the proteins that adhere to each other), she confirmed that Rad21 and Stag3 are complicated, revealing a new type of cohesion, which they referred to as Stag3-Cohesin.

To find out what this new complex does, the researchers invented two types of genetically modified SSCS in the laboratory: one group that completely lacks Stag3, while the other contains only Stag3 (without Stag1 or Stag2). Discover that Stag3-Cohesin is responsible for unusually normal DNA borders in SSCS. More importantly, in mice lost in mice, SSCS was unable to advance from the state of the stem cell to the next stage of sperm development in an effective way. This has led to a fertility problem, which indicates that Stag3-Cohesin does more than the DNA regulation, which is very important to develop appropriate bacterial cells.

Since Stag3 works in the divided cells in the form of mitigation, the team then investigated whether it may also work in other types of human cells. By analyzing large data groups for all types of human cells, they found that Stag3 is highly expressed in immune cells and in lymphoma B-elect, a type of leukemia. Interestingly, the Stag3 ban caused the growth of these lymphoma cells more slowly in laboratory studies, indicating that Stag3 can be explored as a potential goal for future cancer research.

Expectations

This study revealed Stag3-Cohesin as a new type of protein complex that regulates the DNA, which works completely different from the previously known complexes. Because of its unique characteristics, more research on this complex is expected to apply to how genetic activity controls the DNA regulation. One of the most striking discoveries was that changing Stag3 levels could change the percentage of stem cells in the testicle. This indicates a new mechanism that regulates the SSC condition on the border between the division of normal cells and the beginning of the mechanical division.

Besides the bacterial cells, the discovery of the Stag3 prohibition slows the growth of the BC cells indicates a possible role for Stag3 in future cancer research. Although more research is needed to detect accurate mechanisms, these results provide new visions that can offer stem cell biology, reproductive medicine and cancer treatment.

Reciprocal

• Sperm stem cells (SSCS): Stem cells in the testicle that renew themselves and also distinguish to lead to the appearance of sperm.
• DivisionThe process by which the cell produces identical copies of itself, which leads to daughter cells with the same genetic information.
• Divide divisionA specialized form of the unique division of bacterial cells, through which sperm or eggs are created.
• Isolation: “The border” within the 3D structure of the DNA. They prevent reinforcements (DNA elements that help operate genes) from affecting genes across the border, and effectively dividing the genome into separate functional areas.
• B cells: Immune cells that play a major role in producing antibodies within the immune system.
• Cohesin Complex: A routine -shaped protein complex that combines chromatoids together and helps to regulate the DNA in essential rings to regulate genes and division.