过早衰老 z-bo 2020-10-30 321

　　It is well known that the molecules that accumulate at the ends of chromosomes play a key role in preventing DNA damage. Now, in a new study, researchers from the Swiss Federal Institute of Technology in Lausanne have revealed how these molecules are targeted to specific parts of the chromosome---this discovery may help to better understand aging and cancer. The process of regulating cell survival.

　　Just like the metal ornaments at the ends of shoelaces can prevent the ends of shoelaces from fraying, DNA fragments called telomeres form protective caps at the ends of chromosomes. But as cells divide, telomeres become shorter and shorter, which makes the protective cap less effective. Once the telomeres become too short, the cell stops dividing. Telomere shortening and dysfunction are associated with cell aging and age-related diseases including cancer.

　　Scientists already know that an RNA molecule called TERRA helps regulate the length and function of telomeres. In 2007, Claus Azzalin, a postdoctoral researcher in the research team of Professor Joachim Lingner of the Federal Institute of Technology in Lausanne, discovered TERRA. TERRA belongs to non-coding RNA (ncRNA). ncRNA does not express protein, but functions as a structural component of chromosomes. TERRA accumulates at the ends of chromosomes and signals that telomeres should be elongated or repaired.

　　However, it is unclear how TERRA reaches the end of the chromosome and stays there. Lingner said, “telomeres only account for a small part of the total amount of chromosomal DNA, so the question is'how does this RNA find its home?'” To solve this problem, Joachim Lingner's team at the Federal Institute of Technology Lausanne and the Czech Republic The Lumir Krejci team at Masaryk University set out to analyze the mechanism of TERRA accumulation on telomeres and the proteins involved in this process.

　　find home

　　By visually observing the TERRA molecule under a microscope, these researchers discovered that a small segment of this RNA molecule is the key to bringing it to the telomeres. Further experiments showed that once TERRA reaches the end of the chromosome, several proteins regulate its binding to telomeres. Lingner said that among these proteins, a protein called RAD51 plays a particularly important role.

　　As we all know, RAD51 is an enzyme involved in the repair of broken DNA molecules. This protein also seems to help TERRA attach to telomere DNA, forming so-called "RNA-DNA hybrid molecules." Scientists believe that this reaction leading to the formation of a three-stranded nucleic acid structure mainly occurs during DNA repair. This new study shows that when TERRA binds to telomeres, it can also occur at the ends of chromosomes. "Lingner said, "This will trigger change. "

　　These researchers also found that short telomeres are much more efficient at recruiting TERRA than long telomeres. Although the mechanism behind this phenomenon is unclear, they speculate that they will recruit TERRA molecules when either DNA damage or too many cell divisions cause telomeres to become too short. This recruitment is mediated by RAD51, which also promotes telomere elongation and repair. Lingner said, "TERRA and RAD51 help prevent accidental loss or shortening of telomeres. This is an important function."

　　Lingner said that in view of the role of telomeres in health and disease, to observe how this newly discovered mechanism---derived from the observation of living cells and reproduced in a test tube---how it is affected in a very complex cellular environment Regulation will be very important. He said, "We have proposed a model that is supported by the data we have obtained, but in science, we often find that this model must be modified. Of course, there may be more surprises."

　　Next, his team plans to solve other key issues, including whether RAD51 mediates the binding of other non-coding RNAs to chromosomes. These researchers also aim to better describe the mechanism that mediates the binding of TERRA to chromosomes and reveal the functions achieved by this combination. Lingner said, "There are many issues that remain unresolved."