Protection for ends
The secret of eternal youth of stem cells is revealed
Scientists have discovered a unique biological mechanism by which stem cells protect the ends of chromosomes, which allows them to function effectively for many years. The results of the study are published in the journal Nature (Ruis et al., TRF2-independent chromosome end protection during pluripotency).
The chromosomes of human cells carrying hereditary information have special structures at the ends – telomeres, which protect DNA and ensure healthy cell division. In the cells of young people, this protection is very effective, but with age, telomeres become shorter and eventually lose their protective functions. Cells stop dividing and the body ages.
It is known that the telomeric repeat-binding factor 2 (TRF2) protein helps to protect telomeres, which forms a so-called T-loop at the ends of chromosomes. If the TRF2 protein is removed, the ends fuse together, which leads to the formation of "spaghetti chromosomes" and cell death.
Chromosomes with red-highlighted telomeres in a normal cell (top) and fusion of chromosomes in a cell with a knocked-out TERF2 gene (bottom). Drawings from the press release of Francis Crick Institute Researchers discover the unique way stem cells protect their chromosome ends - VM.
Biologists have been actively studying the protective mechanism of telomeres and the TRF2 protein for the past two decades, as it is crucial for understanding the processes of aging and cancer.
Working on this issue, British scientists from the Francis Crick Institute, together with Australian colleagues from the University of Sydney, to their surprise found that stem cells use a completely different mechanism to protect chromosomes.
By removing the TRF2 protein from mouse embryonic stem cells, they saw that T-loops continued to form, the ends of chromosomes remained protected, and the cells remained intact.
As embryonic stem cells differentiate into somatic cells, this unique end-protection mechanism is lost, and the protection of chromosome ends begins to depend on TRF2. According to the authors, this suggests that stem and somatic cells, which include all cells except stem and gametes, protect the ends of chromosomes in fundamentally different ways.
"Now we know that TRF2 is not needed for the formation of a T-loop in stem cells. We assume that there is some other factor that does the same job or another mechanism for stabilizing T-loops in stem cells and which is different from somatic cells," the words of the first author of the article, Phil Ruis, a graduate student of the laboratory for restoring the metabolism of double cells, are quoted in a press release from the Francis Crick Institute. strands of DNA.
Scientists have not yet found out how the alternative mechanism of chromosome protection works, but they have answered the question about the role of T-loops, which has worried biologists for many years. The authors proved that telomeres in stem cells with T-loops, but without TRF2, are also protected, therefore, the T-loop structure itself performs a protective function.
"Our results do not contradict long-term studies of telomeres, but clarify them. In fact, we have shown that stem cells protect their chromosomal ends differently than previously thought, but this still requires a T-loop," says study leader Simon Boulton.
According to the researchers, a better understanding of how telomeres work and how they protect the ends of chromosomes will provide important information about cellular processes that lead to premature aging and cancer.
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