Cell: Reveal How Tissue Protects DNA From Damage Under Mechanical Pressure

- May 02, 2020-

In daily life, our tissues, such as skin and muscles, are stretched, stretched, and compressed without damaging cells or DNA. A team of researchers led by the Max Planck Institute Institute for Aging Biology, the CECAD Excellence Group at the University of Cologne, and Sara Wickstrom at the Institute of Life Sciences at the University of Helsinki have now discovered the mechanisms by which cells protect themselves from these stresses, including the nucleus Transform and soften the genetic material itself.

Protecting the genetic code in our DNA is vital to human health. DNA mutations can cause a variety of diseases, such as developmental disorders or cancer. The chief scientist of the study, Michele Nava, said: "Most of our tissues contain tissue-specific stem cells, which are a type of long-lived cells whose function is critical to tissue function and maintenance. Because they have a long life span, they are effectively protected The genome of these cells is not affected by mutations to prevent cancer and other diseases, which is very important. We already know a lot about the role of chemicals and radiation in inducing DNA damage, but how mechanical force damages DNA, And what mechanism exists to protect our cells from such damage, so far we do not know. "

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Image source: Cell

To study how the DNA in stem cells responds to mechanical deformation, Nava, Miroshnikova and colleagues used a special mechanical device that exposes skin and muscle stem cells to mechanical stretching similar to what they experienced in tissues Conditions. Due to stretching, the nucleus and DNA are reorganized, and at the same time, their mechanical properties are changed and become softer. "We can change the mechanical properties of DNA by applying mechanical force to stem cells. This discovery is exciting. Even more amazing is that if we prevent this change through experiments, the stem cells will now be damaged by DNA, which shows that we have discovered An important protection mechanism. "Yekaterina Miroshnikova said that she led the study with Nava and Miroshnikova.

Direct oneself in the direction of force

When deeply studying the cellular mechanism of stem cells' response to stretching, Nava, Miroshnikova and colleagues found that if exposed to mechanical stretching for a longer period of time, the entire tissue will move in the direction of force. This tissue-scale positioning prevents the deformation of the nucleus and its DNA and restores them to their original state. This tissue-level orientation therefore becomes a long-term mechanical protection.

Finally, the researchers also noted that due to differences in the levels of key nuclear proteins, cancer cells are less sensitive to mechanical stretching than healthy stem cells. Sara Wickstrom said: "Interestingly, the two core characteristics that define cancer are their genetic instability, that is, frequent acquisition of new mutations, and their insensitivity to external signal control. A major goal for our laboratory in the future It is to understand how the defects in this newly discovered pathway can promote the formation of cancer, and how cancer can use these mechanisms to escape tissue control mechanisms. "